Objective. To perform a systematic review of clinical effectiveness and safety of anakinra in rheumatoid arthritis (RA). Methods. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and the reference lists of included articles for randomized controlled trials comparing anakinra to placebo in adults with RA. Results. Five trials involving 2846 patients, 781 randomized to placebo and 2065 to anakinra, were included. There was a significant improvement in the number of participants achieving American College of Rheumatology (ACR)20 (38% vs 23%) treated with anakinra 50-150 mg daily versus placebo after 24 weeks. ACR50 (18% vs 7%), ACR70 (7% vs 2%), Health Assessment Questionnaire, visual analog scale for pain, Larsen radiographic scores, and erythrocyte sedimentation rate all demonstrated significant improvement with anakinra versus placebo as well. There were no statistically significant differences noted in the number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). An increase in incidence of serious infections in anakinra versus the placebo group (1.8% vs 0.6%) was noted that may be clinically significant. Injection site reactions were significantly increased, occurring in 71% of anakinra versus 28% of placebo group. Conclusion. Anakinra is a relatively safe and modestly efficacious biologic therapy for RA. More studies are needed to evaluate safety and efficacy, especially in comparison to other therapies, and adverse event data for the longterm use of anakinra have yet to be assessed. The Journal of Rheumatology Copyright © 2009. All rights reserved.