The aim of this study was to investigate the efficacy of rituximab, a monoclonal antibody that depletes circulating CD20+ B lymphocytes, in relapsing remitting multiple sclerosis (RRMS) patients with inadequate response to disease-modifying therapies. This single group quasi-experimental study recruited RRMS patients who were referred to Sina Farshchian Hospital, Hamadan, Iran, from March 2018 until August 2019. After getting informed consent from the patients, demographic data and duration of disease were recorded. Patients received 500 to 1000 mg of intravenous rituximab every 6 months until 18 months. Relapse rate per year and expanded disability status scale (EDSS) were obtained at baseline and throughout the post treatment follow-up. A total of 70 RRMS patients with the mean age 40.25 ± 8.17 were studied. At baseline, the mean of EDSS and relapse rate was 5.3 ± 1.08 and 0.95 ± 0.64, respectively. After 18 months treatment with rituximab, the relapse rates were significantly reduced (p < 0.000), but the mean EDSS almost remained unchanged (5.7 ± 1.4). Infusion-related adverse effects occurred in 60% of patients in first infusion, and most of them were mild. This study has indicated that rituximab can markedly reduce relapse rates in RRMS patients. The effect of rituximab on EDSS appears to be inappreciable. Also according to our results, administration of rituximab is safe and well tolerated.