Background: This study was performed to compare the effects of low dose interferon beta-1 (IFN-β-1) (CinnoVex, 30 mcg) and high dose IFN-β-1 (REBIF, 44 mcg) on the reduction of the number and size of plaques in magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS).Methods: This historical cohort study, which was performed in 2014 in Sanandaj (western part of Iran). 43 MS patients in two groups were investigated. The first group, which included 19 patients, was treated using high dose IFN (44 mcg) and the second group, which was consisted of 24 patients, was treated using low dose IFN (30 mcg). Patients’ data were collected and analyzed by the Stata version 11 software; the analyses were performed using statistical t-test, chi-square test, Fisher test, and logistic regression.Results: Both drugs were effective in controlling active demyelinating plaque and in preventing plaque activation (P = 0.633). The impact of both drugs in the reduction of the number and size of plaques was evaluated. Based on the results of the MRI, high dose IFN therapy was more effective than the low dose IFN drugs and had a better performance in terms of reducing the number of plaques and in stop-and-recovery (P = 0.039), as well as in reducing the plaque size (P = 0.050).Conclusion: The high dose IFN therapy was more effective than the low dose IFN therapy in reducing the number and size of brain plaques in patients with relapsing-remitting MS (RRMS).