Background: The beneficial effects of the injected disease-modifying drugs (DMDs) in relapsing-remitting Multiple Sclerosis have been previously reported. However the results related to disability outcomes and the reduction of disease progression in the pivotal trials and few longer studies are variable and inconclusive. Objectives: To determine the utilization and the disability outcomes of the DMDs on relapsing-remitting Multiple Sclerosis over fifteen years. Methods: A prospective open-label cohort of 262 clinical definite patients, 78 men and 184 women, with two attacks in the past two years and a disability level DSS≤5.5 were enrolled consecutively from December 1997 to November 1999. A descriptive analysis of the cohort and individual drugs outcomes were performed. The results were compared to natural history studies of Multiple Sclerosis as controls. Results: At 15 years, one-seventh, 38/262 (14.5%) remain on the initial prescription, Betaseron, 15/131 (11.5%), Copaxone, 16/102 (15.5%) and Rebif 7/28 (25%), Avonex 0/1. 223(63.6%) had discontinued at a mean duration of 5.5(SD=4.7) years. 95/262 (36.4%) remain on a drug after switches. The DSS levels of the individual DMDs were analyzed. Conclusion: One-seventh of participants remained on their first prescription. Because of low adherence, the impact of DMDs on disease progression in the longer term cannot be verified.