The systematic review involved a comprehensive search across five databases, MEDLINE, Embase, Scopus, Cochrane Library, and PsycInfo, to identify studies on interventions aimed at reducing vaccine hesitancy. For the purpose of this review, Europe was operationally defined as the WHO European Region, while North America was limited to the United States and Canada, which were the countries included in the eligibility criteria. The search, updated on July 23, 2024, included studies with no temporal restrictions. The full search strategies for all databases are provided in Supplementary Table S1, including the complete search strings used for each database. The eligibility criteria for study inclusion were defined according to the PICOS framework (Population, Intervention, Comparators, Outcomes, and Study design/Setting). The population included community-based samples of the healthy general population, such as adults, parents, or mixed-age populations. Studies focusing exclusively on high-risk clinical groups (e.g., immunocompromised individuals, pregnant women, or people with specific chronic conditions) or narrowly defined professional subgroups (e.g., healthcare workers within a single institution) were excluded. This decision was made to avoid combining populations with substantially different baseline risks, healthcare pathways, and access to vaccination, thereby improving the external validity of the findings for the general population. The interventions considered were strategies aimed at reducing vaccine hesitancy or increasing vaccination uptake. The comparators included no intervention or alternative interventions when available. The outcomes of interest were vaccination uptake and vaccination intention. Eligible study designs included randomized controlled trials (RCTs), cohort studies, and controlled before–after studies. Only English-language articles published before July 4, 2024, were considered. A summary of the eligibility criteria according to the PICOS framework is provided in Supplementary Table S2.

Results from the searches were exported as a Research Information Systems file (.ris) and imported into Rayyan, for title and abstract screening. Abstracts and full-text articles were independently screened by five reviewers (FP, CL, CB, LV and ACD) for eligibility. Any disagreements were resolved through discussion or through adjudication by a senior reviewer, if required. Data extraction was undertaken using a data extraction template by 5 authors (FP, CL, CB, LV and ACD), using Microsoft ExcelThe extracted data included information on authors, publication year, study characteristics (country, design, setting, target population and key sociodemographic features such as age distribution and education level when reported), interventions, control groups, and key results.

Studies were categorised by study type, study scale (local/regional vs. national), and vaccination type. The target populations were grouped into parents, adults, and the general population, which included different adult age groups like young adults (individuals aged 18–35) and the elderly (individuals aged over 75).

In line with widely used public health and behaviour change frameworks, we classified all interventions into four main categories: information-oriented, motivation-oriented, incentive-based, and mandatory interventions. This taxonomy reflects different primary mechanisms of action for changing vaccination behaviour, ranging from providing information and shaping attitudes to altering the external environment through incentives or requirements. Information-oriented interventions were defined as those primarily aimed at increasing knowledge or correcting misinformation about vaccines (e.g., educational materials, public information campaigns, factual web content). Motivation-oriented interventions were those designed to influence attitudes, emotions, social norms or personal commitment towards vaccination (e.g., motivational interviewing, narrative messages, tailored counselling, social norm feedback). Incentive-based interventions offered financial or non-financial rewards or removed costs to encourage vaccination (e.g., vouchers, monetary incentives, facilitated access or reminder programmes framed as benefits). Mandatory interventions relied on laws, regulations or organisational policies that made vaccination a requirement or attached consequences to non-vaccination (e.g., school-entry mandates, certification policies, employment requirements). Digital tools (e.g., websites, apps, SMS, social media, electronic health record prompts) were coded as delivery channels and could be used in any of the four categories; classification was based on the dominant content and mechanism of action rather than on the medium of delivery. This structured categorization facilitated clearer analysis and interpretation of the data, enabling a more effective evaluation of how different interventions impacted vaccine hesitancy and uptake.

Moreover, studies were stratified into two categories based on their scale: large-scale population-based studies and small-scale localized studies. Large-scale studies were defined as those involving interventions implemented at the national level, while small-scale studies focused on interventions conducted at regional or local levels.

For each included study, we extracted information on the outcome measurement instruments. For vaccination intention and related psychological constructs (e.g., hesitancy, trust, perceived risk), we recorded how outcomes were operationalised, including whether they were assessed with single items or multi-item questionnaires and any details reported on the response scale. When authors explicitly reported the use of validated instruments, this information was recorded. In particular, when available, we noted the use of validated scales commonly employed in vaccine hesitancy research, such as the Parent Attitudes about Childhood Vaccines (PACV) scale or other standardized questionnaires. However, several studies relied on single-item measures or study-specific instruments, contributing to heterogeneity in outcome assessment across studies.

For vaccination uptake, we extracted how the outcome was defined in each study as reported by the original authors. Studies were categorised as efficacious or inefficacious according to the conclusions reported by the authors of the included studies regarding the efficacy of the considered intervention on vaccination uptake or vaccination intention. For the purpose of synthesis, studies were classified as efficacious when the intervention produced a statistically significant improvement in vaccination uptake or vaccination intention (two-sided p < 0.05), or when the original authors reported a positive effect of the intervention on the outcome of interest. Studies reporting no statistically significant change or a negative effect were classified as inefficacious.

Where available in the original studies, we extracted effect size measures (e.g., mean differences, standardised mean differences) and any reported 95% confidence intervals. For studies that did not provide effect estimates or confidence intervals, we relied on the statistical tests or p-values reported by the authors to determine whether the intervention produced a statistically significant effect (two-sided p < 0.05). Because effect size reporting was inconsistent across studies and outcome definitions varied substantially, we did not perform additional effect size calculations or meta-analytic pooling.

Risk of bias was assessed for all included studies using the Revised Cochrane Risk-of-Bias tool for randomized trials (RoB 2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for non-randomized studies. The assessment was conducted independently by two reviewers, and any disagreements were resolved through discussion or consultation with a third reviewer. The overall risk-of-bias judgment for each study was determined according to the criteria specified in the respective tools.

The database searches identified a total of 1,341 studies, among which we selected 563 unique studies after removing duplicates. Following title and abstract screening, 463 papers were excluded. The initial screening process yielded 100 articles for further assessment against additional exclusion criteria. During the full-text screening stage, 37 articles were excluded for the following reasons: wrong country (n = 9), wrong population (n = 3), wrong study design (n = 12), wrong outcome (n = 6), wrong publication type (n = 5), and wrong intervention (n = 2). Finally, a total of 59 studies [20–50], [51–78] were included in the review. A PRISMA flowchart diagram illustrating the article selection process is presented in Figure 1.

The systematic review encompassed studies published between 2013 and 2024 (Table 1). The period from 2021 to 2024 saw the highest number of publications, with 16 studies published in 2022 and 14 in 2023. The studies were conducted in North America (United States and Canada) (n = 34) [23, 25–28, 30–33, 35, 36, 39–42, 45, 46, 48, 51, 54–56, 58–60, 62, 66, 68, 69, 72, 74, 75, 77, 78] and in countries within the WHO European Region (n = 30) [20–22, 24, 29, 36, 38, 40, 44, 50, 52, 61, 63–65, 67, 70, 71, 73, 76], (Figure 2). The included studies were predominantly RCT (n = 46) [20–23, 26–31, 34, 35, 37–39, 41–43, 45, 47–49], [51–57, 59, 61, 62, 64–68, 70, 71, 73–79], followed by before-and-after study (n = 11) [24, 25, 32, 33, 36, 44, 46, 50, 58, 63, 72] and cohort study (n = 2) [40, 69].

COVID-19 immunizations were the predominant focus (n = 32 [20, 21, 27, 29, 31, 32, 34, 35, 37, 39–43, 45–51, 54, 58, 59, 61, 68, 73, 75–79], 45%), followed by pediatric vaccinations (n = 10 [22, 30, 38, 52, 62, 63, 65, 67, 71, 72], 16.7%), respiratory vaccines including influenza (n = 10 [23, 26, 32, 36, 39, 47, 51, 53, 70, 73], 11.7%), and Human Papillomavirus (HPV) vaccines (n = 4, 8.3%) [44, 55, 57, 69]. The remaining 7 studies (12%) [24, 25, 28, 56, 64, 66, 74] addressed other vaccine types (Figure 3).

Outcome measures and instruments varied across studies and are summarised in Tables 2, 3.

The efficacy of the various interventions is summarized in Tables 2, 3, which presents outcomes for vaccination uptake and vaccination intention. A substantial majority of studies (n = 44) [20, 23, 25, 27, 30–41, 43–46, 48, 50–53, 55–59], [62–64, 66, 67, 69, 70, 72–77, 80] reported statistically significant results.

This systematic review provides information on the efficacy of interventions aimed at reducing vaccine hesitancy, offering an updated perspective on the topic previously outlined in several documents mostly published before the onset of the COVID-19 pandemic [81], and novel insights specifically focused on strategies for Western countries. We summarised evidence from 59 experimental studies covering a range of vaccination types, with a predominance of interventions related to COVID-19, followed by paediatric and respiratory vaccines. Main findings suggest that information- and motivation-oriented interventions were generally the most efficacious in improving participants' vaccination intentions and increasing vaccine uptake, compared with incentive- and mandatory interventions, which showed mixed or limited results. Furthermore, while no differences in efficacy were observed according to the type of vaccination targeted by the interventions, the increasing adoption of digital tools proved to be a promising strategy to tackle vaccine hesitancy, with strongest evidence in favour of video-based interventions and the rise of new approaches such as chatbots and virtual reality systems.

The geographical distribution of the included studies was predominantly concentrated in the USA and the UK, with most studies published recently. Different vaccination types were considered, with a major focus on SARS-CoV-2 vaccinations (45% of studies). The emphasis on SARS-CoV-2 related interventions is evidently caused by the urgent need for successful strategies aiding the widespread adoption of vaccines during the COVID-19 pandemic. This analysis also shows that the growth in number of publications seen during the 2020–2023 period was exclusively driven by research about SARS-CoV-2 vaccination, while the number of studies addressing the hesitancy for other vaccines remained relatively stable over the years.

The majority of the included studies focused on information-oriented and motivation-oriented campaigns, with generally positive results in terms of efficacy. These findings are consistent with a previous systematic review by Jarrett et al, which suggested that dialogue-based interventions, together with multi-component interventions, show better results in addressing vaccine hesitancy than incentive-based and reminder/recall-based interventions [81]. Among the included studies, Galasso et. al found that public health messages based on altruistic messages about protecting individuals, population health and the economy had significantly positive and sustained effects on increasing vaccination intentions, compared with message narratives about self-protection, which had no effect on vaccination uptake [40]. Another study, Zapf et al 2024, showed that receiving a fact-based intervention did not have a negative impact on vaccination intention, whereas narrative-based framing (i.e., information was provided via a story-telling format) appeared to have a negative impact [77]. In particular, it significantly reduced the intervention’s effectiveness compared to no framing (DiD = −0.15; 95% CI: −0.27 to −0.03; p = 0.014), possibly due to psychological reactance, where individuals perceive persuasive narratives as threats to their autonomy and thus resist the message [82]. Overall, our review found that both information-oriented and motivation-oriented approaches are efficacious, although we did not find sufficient evidence to determine whether one is more successful than the other in reducing vaccine hesitancy.

With regard to interventions based on incentive programmes, we found mixed results in terms of overcoming vaccine hesitancy. Four of the 6 included studies reported an increase in vaccine uptake. A notable example of this is represented by the study of Fishman et al., which examined various types of financial incentives concluding that guaranteed cash performed better than lottery-based incentives, and that the amount of money promised may be less important than the timeliness of the reward or the message framing when communicating about the incentives [31]. The validity of incentive-based interventions on vaccination uptake has been also reported by another recent systematic review [16], that identified this type of strategy as the most promising among all those evaluated. On the other hand, results about the impact of incentive-based interventions on vaccination intention are scarce, since only one of the 6 studies examined this outcome [65]. It’s interesting to note that this study shows that financial incentives don’t have an impact on vaccination intention both in the negative nor in the positive sense. This means that they are not reported to reduce vaccine hesitancy per se, but that they also do not affect the belief that vaccines are safe, nor people’s trust in researchers, the public health agency and pharmaceutical companies.

Finally, our findings indicate that mandatory vaccination appears to be the least efficacious strategy. Even though the number of studies using this strategy was also very low (only 3 out of 59), evidence suggested that neither vaccination intentions nor vaccination uptake improved after the implementation of this strategy. For example, the study performed by Betsch et al., reported that this type of strategy could be especially inefficacious toward individuals with a negative vaccination attitude, for whom vaccination uptake decreased by 39% after the institution of compulsory vaccination (compared to a decrement of 8% for individuals with a positive attitude towards vaccines) [22]. Although mandatory vaccination has historically proven to be effective in increasing vaccination coverage, some authors have argued that in the long term, vaccine mandates may have a negative impact on vaccination intentions and vaccine hesitancy, highlighting the importance of implementing behavioural and public trust promotion strategies [83, 84]. This is consistent with findings of another systematic review by Batteux et al. which suggested that the introduction of mandatory vaccination may have a negative impact, particularly on individuals' intention to vaccinate [34]. However, it should also be noted that, regardless of the type of approach used, the impact of the interventions on attitudes towards vaccination and vaccine uptake was found to be variable, due to differences in cultural contexts and countries of implementation, as well as the target group involved and their baseline vaccination intentions.

We also report that the majority of the included studies (36 out of 59) adopted digital modalities to conduct the interventions. In particular, our results show that video-based interventions were the most efficacious (10%–20% increases in vaccination uptake). Other successful digital interventions were conducted by the use of mHealth applications, online education programs/modules, and internet-based interventions. In a previous systematic review, text messaging, accessing immunisation campaign websites, web-based patient portals and computerised reminders were found to increase immunisation coverage, but there was insufficient evidence on the efficacy of using social networks, email communication and smartphone applications [85]. Meanwhile, in a subsequent study, we found that email-based reminder/recall interventions were efficacious in increasing vaccination coverage compared with no intervention, with potential for cost reduction, improved performance through automation, and effective outreach to target populations, although data for robust evidence of superiority over traditional methods were still limited [86]. Indeed, according to previous analysis, current adoption of digital technologies in immunisation programmes across Europe remains fragmented. Thus, identifying best practices and common standards for digital interventions to be successfully implemented in national vaccination strategies is necessary to support the need for effective lifelong immunisation services [87–89].

This study identified promising digital strategies to combat vaccine hesitancy, including the use of advanced technologies like chatbots and Virtual Reality. Altay et al. found that a chatbot providing information on COVID-19 vaccines significantly boosted vaccination intentions and improved attitudes toward vaccination [20]. Virtual reality was used in two studies. Real et al. created an immersive virtual reality curriculum to teach physicians communication skills when discussing vaccine hesitancy, resulting in a decrease in the rate of influenza vaccine refusal among patients being counselled in the period following the curriculum compared to the control group [59]. Vandeweerdt et al. investigated the effect of a first-person experience through immersive virtual reality on vaccination intentions; the motivational virtual reality intervention was almost three times more efficacious than communicating the same content through text and images [71].

National and local interventions to reduce vaccine hesitancy varied in scale, efficacy, and duration. Large-scale national strategies led to modest improvements in uptake (1.2%–17.1%) and reductions in avoidance (2.3%–29.6%). Small-scale interventions showed greater variability, with uptake increases from 3% to 30% and hesitancy reductions from 2.6% to 33%, with few reporting no effect. Interventions ranged from short-term (weeks/months, often for seasonal or emergency needs), to medium-term (months to a year, supporting community engagement for routine immunisations), to long-term (multi-year, for vaccines with multiple doses or targeting specific age groups, such as HPV).

This review has several limitations. Evidence was restricted to the WHO European Region and North America (United States and Canada) and studies targeting high-risk clinical groups were excluded, limiting the generalisability of findings. The general population itself was heterogeneous, and many studies lacked detailed sociodemographic data, preventing subgroup analyses. Considerable heterogeneity in interventions, settings, vaccines, outcomes and methods also precluded a quantitative meta-analysis. A consistent intention–behaviour gap emerged, with improvements in attitudes not always translating into higher uptake, likely due to structural and practical barriers. Most included studies were conducted during the COVID-19 period, where concurrent public health measures may have influenced hesitancy, reducing generalisability to other vaccines. Publication bias is possible, and relying on the term “vaccine hesitancy” in the search strategy may have missed relevant studies. In addition, the restriction to English-language publications and to specific study designs may have excluded relevant evidence from other contexts or methodological approaches.

Despite these limitations, this review provides one of the most comprehensive assessments of experimental interventions in Europe and North America. Future research should use standardised outcomes and validated measurement tools, broaden geographic and vaccine coverage, include subgroup analyses, and evaluate interventions in real-world contexts. Validated scales, such as the PACV and Vaccine Confidence Scale, are particularly important for accurately measuring changes in vaccine hesitancy [90]. Although this review focuses on Europe and North America, the identified strategies may provide useful insights for vaccination policies in other regions. However, the implementation of these interventions should be carefully adapted to local sociocultural contexts and health system characteristics.

This review indicates that interventions reducing vaccine hesitancy in Europe and North America are most effective when they provide clear information or use motivational strategies, particularly through digital formats such as videos and web-based platforms. Across 59 experimental studies, these approaches improved vaccination uptake and intention, with increases of 1.2%–30% and reductions in hesitancy up to 33%. Video-based and mHealth interventions were especially effective. Mandatory measures sometimes increased uptake but often reduced intention, while incentives had limited impact on attitudes and only short-term effects on uptake. Overall, trust-building, context-specific strategies appear preferable to coercive approaches. Future work should use standardised measures, include a broader range of vaccines, and evaluate interventions in real-world settings.