Abstract Background Dimethyl fumarate and fingolimod are oral disease modifying treatments (DMTs) that reduce relapse activity and slow disability worsening in relapsing–remitting multiple sclerosis (RRMS). Objective To compare the effectiveness of dimethyl fumarate and fingolimod in a real-world setting, where both agents are licensed as a first-line DMT for the treatment of RRMS. Methods We identified patients with RRMS commencing dimethyl fumarate or fingolimod in the Swiss Federation for Common Tasks of Health Insurances (SVK) Registry between August 2014 and July 2019. Propensity score-matching was applied to select subpopulations with comparable baseline characteristics. Relapses and disability outcomes were compared in paired, pairwise-censored analyses. Results Of the 2113 included patients, 1922 were matched (dimethyl fumarate, n = 961; fingolimod, n = 961). Relapse rates did not differ between the groups (incident rate ratio 1.0, 95%CI 0.8–1.2, p = 0.86). Moreover, no difference in the hazard of 1-year confirmed disability worsening (hazard ratio [HR] 0.9; 95%CI 0.6–1.6; p = 0.80) or disability improvement (HR 0.9; 95%CI 0.6–1.2; p = 0.40) was detected. These findings were consistent both for treatment-naïve patients and patients switching from another DMT. Conclusion Dimethyl fumarate and fingolimod have comparable effectiveness regarding reduction of relapses and disability worsening in RRMS.