INTRODUCTION: Hepatitis B (HB) vaccination programs were set up worldwide in the early 1990s. Despite their major focus on reducing the burden of HB infection, they have seldom achieved the targeted population coverage in most countries, including the USA, with around 24.5% of adults being vaccinated against HB. Among proposed reasons for this is the persisting doubt about a possible link between HB vaccination and the occurrence of cases of multiple sclerosis (MS). OBJECTIVE: Our objective was to evaluate a potential safety signal between MS and HB vaccination. We conducted a disproportionality analysis (DPA) using the cases reported to the Vaccine Adverse Event Reporting System (VAERS). METHODS: We calculated the proportional reporting rate (PRR) and reporting odds ratio (ROR) of MS having occurred within the 120 days following HB immunization in adults aged 19-49 years when compared with other vaccines using the reports recorded in the VAERS database. Both ratios were estimated globally and then according to the origin of reports (USA vs. non-USA). We then performed a sensitivity analysis using a broader category of demyelinating events. FINDINGS: MS cases following HB vaccination were more likely to originate from outside the USA and to be reported before 2000 than those associated with other immunizations. All computed ratios were found to be statistically significant, with PRRs ranging from 3.48 to 5.56 and RORs ranging from 3.48 to 5.62. When considering the geographical origin, similar RORs were obtained for both US and non-US cases. CONCLUSION: In VAERS, MS cases were up to five times more likely to be reported after an HB vaccination than after any other vaccination. Since DPA is mainly suited for hypothesis generation, further studies evaluating the nature of the link between MS and HB vaccination would be of considerable importance.< Réduire