Background and purpose Disease‐modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment. Methods We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. Results Of the 21,189 patients with MS (age 47.1 ± 13.1 years; Expanded Disability Status Scale (EDSS) score 3.4 ± 2.4), 6,631 (31.3%; 95% confidence interval CI 30.7–31.9) were not receiving any DMT. Although patients with a relapsing‐remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95% CI 14.2–15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing‐remitting MS, the main factors explaining never having been treated were: not having ≥9 lesions on brain magnetic resonance imaging (odds ratio OR 0.52 95% CI 0.44–0.61) and lower EDSS score (OR 0.78 95% CI 0.74–0.82). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT. Conclusion A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS. The objectives were to determine the proportion of untreated patients with multiple sclerosis (MS) followed in expert centers in France and to determine the predictive factors of non‐treatment. Among the 21,189 patients with MS, 31.3% were not receiving any disease‐modifying treatment and the most important predictive factor for not being treated was the disease course: 14.8% of patients with a relapsing‐remitting course were untreated, while 50.4% of those with secondary and 64.2% of those with primary progressive MS were untreated. After multivariate analysis among patients with relapsing‐remitting MS, the main factors explaining never having been treated were not having ≥9 lesions on brain magnetic resonance imaging and lower Expanded Disability Status Scale score.