Background - France is among the countries with high prevalence of multiple sclerosis (MS). The most recent estimates are from 2012 and need to be updated because MS prevalence has increased worldwide. Objective - To estimate MS prevalence in France on December 31, 2021 and to describe the characteristics of the French MS population using data from the French national health insurance database (SNDS). Material and methods - Persons with MS (PwMS) were identified in the SNDS database (99% of national coverage) using an algorithm with three criteria: long-term disease status, hospitalizations, and MS-specific drug reimbursements. Crude and sex- and age-stratified prevalence rates were calculated with their 95% confidence intervals as well as the standardized prevalence stratified on the region of residence. Results - In total, 134,062 PwMS were identified (71.8% of women, median age 53.0±14.8years) yielding a prevalence of 197.6 per 100,000 (95% CI [196.5-198.7]). Prevalence rates in women and men were respectively 274.9 (95% CI [273.2-276.6]) and 115.2 (95% CI [114.0-116.4]). In metropolitan France, the highest prevalence rates were observed in the northeastern regions (e.g.>230 PwMS per 100,000 in Grand Est and Hauts-de-France), and the lowest rates in the southwestern regions (∼180 PwMS per 100,000 in Nouvelle-Aquitaine and Occitanie). Overall, 32.1% of PwMS had another long-term disease and 51.8% received at least one MS-specific drug in 2021. Conclusion - MS prevalence in France has increased by ∼30% in the last 10years. This increase is probably linked to population ageing, longer survival of PwMS, and the long observation period. The part attributable to a possible increase in MS risk remains to be determined with incidence studies.