AbstractVaccine‐associated multiple sclerosis (MS) is rare, with insufficient evidence from case reports. Given the scarcity of large‐scale data investigating the association between vaccine administration and adverse events, we investigated the global burden of vaccine‐associated MS and potential related vaccines from 1967 to 2022. Reports on vaccine‐associated MS between 1967 and 2022 were obtained from the World Health Organization International Pharmacovigilance Database (total number of reports = 120 715 116). We evaluated global reports, reporting odds ratio (ROR), and information components (IC) to investigate associations between 19 vaccines and vaccine‐associated MS across 156 countries and territories. We identified 8288 reports of vaccine‐associated MS among 132 980 cases of all‐cause MS. The cumulative number of reports on vaccine‐associated MS gradually increased over time, with a substantial increase after 2020, owing to COVID‐19 mRNA vaccine‐associated MS. Vaccine‐associated MS develops more frequently in males and adolescents. Nine vaccines were significantly associated with higher MS reporting, and the highest disproportional associations were observed for hepatitis B vaccines (ROR 19.82; IC₀₂₅ 4.18), followed by encephalitis (ROR 7.42; IC₀₂₅ 2.59), hepatitis A (ROR 4.46; IC₀₂₅ 1.95), and papillomavirus vaccines (ROR 4.45; IC₀₂₅ 2.01). Additionally, MS showed a significantly disproportionate signal for COVID‐19 mRNA vaccines (ROR 1.55; IC₀₂₅ 0.52). Fatal clinical outcomes were reported in only 0.3% (21/8288) of all cases of vaccine‐associated MS. Although various vaccines are potentially associated with increased risk of MS, we should be cautious about the increased risk of MS following vaccination, particularly hepatitis B and COVID‐19 mRNA vaccines, and should consider the risk factors associated with vaccine‐associated MS.