Background: Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses. Objective: To assess the risk of relapsing-remitting multiple sclerosis (RR-MS) worsening after YFV. Methods: Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS. Results: 128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) ( p = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53–3.30, p = 0.54). Conclusion: These results suggest that YFV does not worsen the course of RR-MS.