Objective: To evaluate the efficacy and safety of rituximab for relapsing-remitting multiple sclerosis. Results: Fifteen studies that collectively included 946 patients were selected for the meta-analysis. Rituximab therapy was associated with the mean annualized relapse rates decreasing by 0.80 (95% confidence interval, 0.45-1.15) and the mean Expanded Disability Status Scale score decreasing by 0.46 (95% confidence interval, 0.05-0.87). The likelihood of patients experiencing a relapse after starting rituximab therapy was only 15% (95% confidence interval, 7%-26%). Although mild-to-moderate adverse events occurred in 29.6% of the patients, there were no severe adverse events. Conclusions and relevance: This systematic review and meta-analysis shows that rituximab is associated with reduced annualized relapse rates and disability levels in patients with relapsing-remitting multiple sclerosis. It is also well tolerated and is not associated with serious adverse events.