The evolution of multiple sclerosis (MS) and the resulting disability are unpredictable. To identify clinical variables that could be potential prognostic factors, we followed a cohort of 288 patients diagnosed as having relapsing-remitting MS between 1990 and 2003. The end point was the first occurrence of a non-reversible EDMUS-GS score >or=3 (moderate disability). The impact of the number of MS attacks during the first 2 years of the disease as well as the first interattack interval were assessed in two Cox models, one using a fixed-in-time covariate, the other using a time-dependent covariate. Older age at onset and a higher number of MS attacks during the first 2 years of MS proved to be predictors of unfavourable prognosis. The first interattack interval had no influence on the evolution of the disability, conversely to the first relapse which had a short-term impact on the prognosis. We confirmed that the age at onset and the number of MS attacks during the first 2 years of MS are predictors of the evolution of the disability and demonstrated the importance of using time-dependent covariates.