Abstract Background Hepatitis A (HepA) global burden is estimated to be > 100 million new cases/year. HepA is vaccine-preventable, but outbreaks still occur in regions with low endemicity such as Europe. Guidelines for HepA vaccination in adult risk groups are available in European countries, but adherence to vaccination recommendations is not systematically documented. Here we review European data on HepA infection outcomes, we discuss the HepA risk in the population in order to assess the adequacy of HepA vaccination strategies. Methods A systematic search in PubMed and Embase was performed from January 2001 to April 2021. Relevant data from ECDC, ProMED, ESCAIDE and national public health websites was also reviewed. We included articles in all languages, covering all ages and data published on 11 countries (Denmark, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland and the United Kingdom [UK]). Studies on seroprevalence and risk factors for HepA virus (HAV) were excluded. Results Overall, 134 articles and 85 grey literature reports were included in our review. In Europe, in the last 20 years, HepA infections were reported in all ages. Annual hospitalization rates exceeded 50% in 8 of the surveyed countries during 2016–2019. HAV complications were reported by 28 publications (ps): 8 liver transplantation cases in 6 ps ; liver failures in 0%–25% of HepA patients reported by 23 ps and hemorrhagic complications in 0%–51% of HepA patients reported by 8 ps. Fatality rates, reported by 12 ps for Italy, Hungary, Denmark, Germany and Spain were 0.05%–0.26%, mostly in adults/older adults. Conclusion In Europe, HepA infections are recorded in all ages despite not being consistently reported. Although the fatality rate is low, the hospitalization rates and the morbidity are high in adults/older adults. Considering the current epidemiological situation and HepA-related costs, authorities should raise awareness on HepA risk and adapt or improve compliance with the vaccination recommendations. Adherence to the existing recommendations should be monitored more closely. Universal HepA vaccination may be considered, similarly to the strategy adopted in the United States after widespread and ongoing HepA outbreaks. Funding GlaxoSmithKline Biologicals SA Disclosures Anar Andani, BSc, Medical director, GSK group of companies: Employee|GSK group of companies: Stocks/Bonds Eveline Bunge, PhD, GSK group of companies: My institution received grants and payment for developing studies Jennifer Eeuwijk, MSc, GSK group of companies: My institution received grants and payment for developing studies George Kassianos, MD (Hons), FRCGP, FESC, FBGTHA, FFTM RCPS(Glasg), FBHS, FHEA, FAcadMEd, DRCOG, LRCP (Edin.), LRCS (Edin.), LRCP&S (Glas.), DMedAcup., DMedHypn., DFP, AstraZeneca: Advisor/Consultant|British Global and Travel Health Association: President|European Scientific Working Group on Influenza (ESWI): Board Member|European Scientific Working Group on Influenza (ESWI): Lectures|MSD: Advisor/Consultant|Northern European Conference on Travel Medicine: Lectures|Novavax: Advisor/Consultant|Pfizer: Advisor/Consultant|RAISE Pan-European Committee on Influenza: Chair|Royal College of General Practitioners: National Immunisation Lead|Sanofi Vaccines: Advisor/Consultant|Seqirus: Advisor/Consultant|UK National Health Service: Lectures|Valneva: Advisor/Consultant Robert Steffen, MD, GSK group of companies: Advisor/Consultant|GSK group of companies: Honoraria.