OBJECTIVES: To estimate the comparative efficacy of oral therapies (fingolimod, dimethyl fumarate [DMF] and teriflunomide) in delaying progression to disability health states in patients with relapsing–remitting multiple sclerosis (RRMS). METHODS: Cox proportional hazards regression models were used to analyse 6-month confirmed disability progression (CDP; based on Expanded Disability Status Scale [EDSS] scores) in the pooled fingolimod FREEDOMS trials. Initial models were constructed with eight baseline covariates as main and treatment-interaction effects and final models with the most predictive covariates were selected using a stepwise algorithm. Models predicted hazard ratios (HRs) for 6-month CDP for fingolimod 0.5mg versus placebo for average TEMSO (teriflunomide trial) and pooled DEFINE/CONFIRM (DMF trials) patients. Time from EDSS score 0 to scores of 4 or 6 and to conversion to secondary progressive multiple sclerosis (SPMS) were estimated by fitting a multi-state Markov Transition model to individual patient data from the pooled FREEDOMS placebo groups (HRs accounted for treatment effects) and the London Ontario cohort (SPMS and RRMS–SPMS transitions). RESULTS: Without covariate adjustment, the HR for CDP for fingolimod versus placebo in the pooled FREEDOMS trials was numerically lower (i.e. fingolimod more efficacious) than that for DMF twice daily versus placebo in DEFINE/CONFIRM (0.62 versus 0.71). In adjusted comparisons, the predicted HR for fingolimod versus placebo in the DEFINE/CONFIRM population was lower than in the FREEDOMS population (initial model, 0.51; final model, 0.60). Fingolimod increased median time to disability health states (EDSS 4, 1.0 years; EDSS 6, 1.5 years) and SPMS (1.9 years) compared with DMF. Comparisons with teriflunomide also showed fingolimod increased times to disability health states. CONCLUSIONS: Fingolimod is the only oral treatment that has demonstrated a significant effect on 6-month CDP in a clinical trial and our modeling approach suggests that progression to severe disability health states is delayed by fingolimod.