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Objective – To evaluate and compare the long-term efficacy and safety of two different β-interferon preparations (IFN- β-1a vs IFN- β-1b). Materials and methods – Two parallel outpatient groups with relapsing–remitting multiple sclerosis (RRMS), according to Poser criteria, were treated with either intramuscular IFN- β-1a 30 μg (group A, n = 62) or subcutaneous IFN- β-1b 250 μg (group B, n = 64). Results – A statistically significant reduction was seen in the relapse rate ( P < 0.0001) in both groups. No significant difference was found between the two groups ( P = 0.43). After 6 years of therapy, the mean Expanded Disability Status Scale score was 3.22 ± 1.47 (Δ 1.03 ± 1.35) in group A and 3.34 ± 1.47 (Δ 0.97 ± 1.47) in group B ( P = 0.47). Conclusions – Our study results suggest that the efficacy of IFN- β-1a 30 μg once weekly and SC IFN- β-1b 250 μg every other day is similar. Both IFN- β-1a and IFN- β-1b are effective in slowing disability progression. [ABSTRACT FROM AUTHOR]