OBJECTIVES: Relapses and disability progression are the clinical hallmarks of MS and the two most commonly assessed endpoints for therapeutic interventions in clinical trials. For many patients relapses are the initial defining feature of MS. However, the accumulation of disability has the greatest long-term clinical, social and economic impact on patients and society. This study evaluated the comparative efficacy of disease-modifying therapies for multiple sclerosis and ranked each therapy based on probabilities of being among the best treatments for each outcome. METHODS: A network meta-analysis was conducted within a Bayesian framework to estimate comparative annualised relapse rates (ARR) and risks of disability progression (defined by both a 3-month, and 6-month confirmation interval). Cumulative ranking analysis, using the Surface Under the Cumulative RAnking curve (SUCRA) method, provided a ranking of treatments for each outcome. RESULTS: Alemtuzumab and natalizumab had the highest SUCRA scores for ARR (>90%) and disability progression confirmed after three months (>80%), while IFN β-1a 30mcg ranked lowest among active treatments for these outcomes. Ranking of treatments was affected by the definition of disability progression largely due to the conflicting results of IFN β-1b 250 mcg, ranking among the most efficacious treatments for disability progression confirmed after six months (>90%) and among the least efficacious for disability progression confirmed after three months (<50%).  Alemtuzumab and natalizumab both scored relatively highly for disability progression confirmed after six months. Notable variation in ranking across outcomes was observed for fingolimod (>70% for ARR, <50% for the disability progression outcomes). CONCLUSIONS: The magnitude of treatment effects and associated uncertainty varied between DMTs, and across outcomes. While natalizumab and alemtuzumab demonstrated consistently high ranking for both relapse and progression, with older interferon-beta and glatiramer acetate products ranking lowest, variation in disability progression definitions lead to variation in the relative ranking of treatments.