OBJECTIVES: To compare confirmed disability improvement in propensity score (PS)-matched cohorts of patients receiving fingolimod or BRACE (beta-interferons or glatiramer acetate) following previous BRACE treatment, who had active multiple sclerosis (MS), using data from two German observational studies, PANGAEA and PEARL, respectively. METHODS: Patients with active MS (≥1 relapse in the year before the study) from the PANGAEA and PEARL registries were included if they had received BRACE before participating in the studies and did not have missing relapse data in the previous year. Patients from the PANGAEA registry were excluded if they had participated in PEARL. Patients in the PANGAEA cohort were matched in a 3:1 ratio to patients in the PEARL cohort using a PS-matching approach. Time to 3-month and 6-month confirmed disability improvement was assessed using a Kaplan–Meier approach. Hazard ratios for confirmed disability improvement (fingolimod vs BRACE) were estimated using a Cox proportional hazards model. RESULTS: After PS matching, a total of 1535 patients were included (PANGAEA, n=1163; PEARL, n=372). The proportions of patients in the PANGAEA and PEARL cohorts with 3-month confirmed disability improvement were 14.6% and 7.0%, respectively (p<0.001). Similar results were seen for 6-month confirmed disability improvement (11.0% vs 6.2%; p<0.001). The probability of 3-month confirmed disability improvement was significantly higher in PANGAEA compared with PEARL (175% increase; HR, 2.75; 95% CI, 1.82–4.15; p<0.001). The corresponding value for 6-month confirmed disability improvement was a 126% increase (2.26; 1.45–3.53; p<0.001). Similar findings were found in subgroups of patients with at least 1 year of follow-up (3-month: 176% increase; 2.76, 1.80–4.22; p<0.001; 6-month: 136% increase; 2.36, 1.50–3.69; p<0.001). CONCLUSIONS: This comparison of real-world cohorts of patients with MS demonstrates that fingolimod treatment is associated with statistically significant increases in the probability of confirmed disability improvement compared with BRACE.