Objective: To examine whether rituximab induction followed by glatiramer acetate (GA) monotherapy is more effective than GA alone for the treatment of relapsing MS with active disease. Methods: This was a single center, double-blind, placebo-controlled study(NCT01569451). Fifty-five participants were randomly assigned (1:1ratio) to either rituximab (R-GA) or placebo induction (P-GA), followed by all participants initiating GA therapy. Participants were followed up to 3-years. The primary endpoint was the number of participants with no evidence of disease activity (NEDA) (those without relapse, new MRI lesions and sustained change in disability. Results: Twenty-eight and 27 participants received rituximab and placebo induction, respectively, with one participant in each arm withdrawing prior to 6-month MRI. There were no significant differences in baseline characteristics. At end of study, 44.44% of R-GA participants demonstrated NEDA, vs 19.23% of P-GA participants (p = 0.049). A smaller proportion of R-GA participants failed treatment (37.04%R-GA vs 69.23%P-GA, p=0.019), and time to treatment failure was longer (23.32 monthsR-GA vs 11.29 monthsP-GA, p=0.027). Fewer participants in the R-GA arm had new lesions (25.93%R-GA vs 61.54%P-GA, p=0.009), and there were fewer new T2 lesions (0.48R-GA vs 1.96P-GA vs, p=0.027). Probability of demonstrating NEDA in the R-GA arm returned to baseline within the study period. There were no differences in adverse events. Conclusions: Induction therapy with rituximab followed by GA may provide superior efficacy in the short term to GA alone in relapsing MS, but this benefit appears to wane within the study period. Larger studies are needed to assess sustainability of results.