The aim of the study was to evaluate how the natural history of multiple sclerosis (MS) had changed over a 15-year period. We compared disability and mortality in a cohort of 83 MS patients hospitalised in the Neurological Institute of Pavia, northern Italy, from January 1, 1990, to December 31, 1991, with a similar cohort of 52 patients analysed in the past. After the follow-up, an unfavourable course (death or relevant disability) was observed in 41% of the patients in the new cohort, compared to 63.5% of the patients in the old one. The percentage of deceased patients was reduced from 25 to 6%. The analysis of the pooled data of the two cohorts indicates a recent tendency of firstly hospitalised patients having a shorter disease duration and a lower disability level, which could explain the relevant decrease both in mortality and disability. Finally, our findings confirmed that age at onset, early disability and a short interval between onset and secondary progression increase the risk of an unfavourable course.