Objective. To perform a systematic review of efficacy and safety of abatacept in patients with rheumatoid arthritis (RA). Methods. We searched the Cochrane Library, MEDLINE, EMBASE, ACP Journal Club, and Biosis Previews for randomized controlled trials (RCT) comparing abatacept alone or in combination with disease modifying antirheumatic drugs (DMARD)/biologics to placebo or other DMARD/biologics in patients with RA. Two reviewers independently assessed search results, risk of bias, and extracted data. Results. Seven trials with 2908 patients were included. Compared with placebo, patients with RA treated with abatacept were 2.2 times more likely to achieve an American College of Rheumatology 50% response (ACR50) at one year (relative risk 2.21, 95% CI 1.73, 2.82) with a 21% (95% CI 16%, 27%) absolute risk difference between groups. The number needed to treat to achieve an ACR50 response was 5 (95% CI 4, 7). Significantly greater improvements in physical function, disease activity, pain, and radiographic progression were noted in abatacept-treated patients compared to placebo. Total adverse events (AE) were greater in the abatacept group (RR 1.05, 95% CI 1.01, 1.08). Other harm outcomes were not significant, with the exception of serious infections at 12 months, which were more common in the abatacept group versus control group (Peto odds ratio 1.91, 95% CI 1.07, 3.42). Serious AE were more numerous in the abatacept + etanercept group versus the placebo + etanercept group (RR 2.30, 95% CI 1.15, 4.62). Conclusion. Abatacept seems to be efficacious and safe in the treatment of RA. Abatacept should not be used in combination with other biologics to treat RA. Further longterm studies and postmarketing surveillance are required to assess for longer-term harms and sustained efficacy. The Journal of Rheumatology Copyright © 2010. All rights reserved.