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Abstract Background With more than 100 million new hepatitis A (HepA) virus (HAV) infections estimated each year, HepA is a serious health concern worldwide. Several countries implemented 2- or 1-dose universal mass vaccination (UMV) programs of children with HAV vaccines. Here we present the first systematic review describing the impact of 2- and 1-dose UMV programs on HepA incidence and related health outcomes. Methods We systematically searched several databases for data published between Jan 2000–Jul 2019 (Figure 1). We assessed available evidence for 2- and 1-dose UMV programs with inactivated HAV vaccine in children worldwide, in terms of impact on HepA incidence, disease severity and mortality, vaccine efficacy, vaccine effectiveness and antibody persistence. Figure 1. PRISMA flowchart Results 3739 articles were screened and 34 studies were included in our analysis (Figure 1). 18 real-world studies in 9 countries showed that HepA incidence declined in all ages following introduction of 2-dose and 1-dose UMV programs and persisted for at least 14 years (2-dose) and at least 6 years (1-dose) (Figure 2). Evidence for 1-dose schedule was limited to only 3 studies. HAV related outcomes (disease severity, mortality) decreased after UMV with either 2-dose or 1-dose schedule. Vaccine effectiveness for the 2-dose schedules was ≥ 95% over 3–5 years. Vaccine efficacy for the 1-dose schedule was > 98% over 0.1–7.5 years. Anti-HAV antibody persistence in vaccinated children was documented up to 15 years with ≥ 90% seropositivity rates for the 2-dose schedule and up to 10 years with ≥ 74.3% seropositivity rates for the 1-dose schedule. Anti-HAV antibody GMC data is presented in Table 1. Figure 2. Impact of vaccination on hepatitis A incidence in countries implementing 2-dose or 1-dose schedules (data from studies presenting ‘all ages’ incidence data) Table 1. Anti-HAV antibody GMCs following vaccination with 2-dose and 1-dose schedules, data from studies included in our review Conclusion The implementation of 2- and 1-dose UMV programs against HAV induced decreases in disease incidence and related outcomes. Experience with 2-dose schedule is extensive, with wide geographical use, while evidence beyond 10 years for the 1-dose schedule has not yet been demonstrated. Continued and robust surveillance is needed to monitor the epidemiology, vaccine effectiveness, antibody persistence and protection (particularly in the absence of natural boosting) in order to have a strong, scientifically sound basis for decision makers when concluding on HepA prevention strategies in their countries. Funding: GlaxoSmithKline Biologicals SA Disclosures Anar Andani, BSc, GSK group of companies (Employee, Shareholder) Eveline M. Bunge, PhD, GSK group of companies (Research Grant or Support) Fernanda Salgado, MD, MSc, GSK group of companies (Employee) Rosa C. van Hoorn, MSc, GSK group of companies (Research Grant or Support) Bernard Hoet, MD, FFPM, GSK group of companies (Shareholder)