We performed an observational, retrospective analysis of outcome in a sequential cohort of patients with relapsing-remitting multiple sclerosis (RRMS) in Argentina. Patients treated for 16 months with interferon beta-1a (Avonex; 30 micrograms intramuscularly, once a week), interferon beta-1a (Rebif); 44 micrograms subcutaneously, thrice weekly), interferon beta-1b (Betaferon; 250 micrograms subcutaneously, every other day) or glatiramer acetate (Copaxone; 20 mg subcutaneously daily) were compared with a non-treated group of patients. The different treatment groups were similar in baseline demographic and clinical variables. A significant fall in the annual relapse rate was observed for all four treatments, with the largest effect observed with glatiramer acetate (81% reduction in relapse rate, compared with pre-treatment values). The proportion of patients remaining relapse-free for the entire 16-month treatment period varied from 37% in untreated patients to 83% in the glatiramer acetate treated group. No statistically significant changes in disability scores were observed over the treatment period. This first such comparative study in Latin America shows that treatment of multiple sclerosis patients with immunomodulatory therapies in the context of current standards of care in Argentina provides clinically important benefit, and suggest that some of these therapies may be better than others.