OBJECTIVES: Rheumatoid arthritis (RA) affects ~1.3 million Americans, accounting for 9 million physician visits and >250,000 hospitalizations annually.  Drug therapy is costly but essential. This study evaluates the cost-effectiveness of golimumab, a recently approved TNF-α inhibitor (TNF-I) compared with existing agents (infliximab, etanercept, adalimumab), when given in combination with methotrexate (MTX) from a third-party payer perspective. METHODS: A Markov model was constructed to follow a hypothetical cohort of 10,000 patients with active RA who received one of the four TNF-I and MTX across patient life-time. The primary effectiveness outcomes were the American College of Rheumatology (ACR)-20 response rates mapped to health assessment questionnaire-scores to derive quality-adjusted life-years (QALYs). ACR-20 rates were derived from a systematic review of efficacy trials. Long-term drug withdrawal rates were derived from observational studies. Data for drug, administration, monitoring, toxicity and RA-related direct costs were derived from the literature. Incremental costs (2011 US$) per QALY were compared between TNF-Is. One-way and probabilistic sensitivity analysis (PSA) techniques were employed to examine effects of various assumptions and parameter uncertainty. RESULTS: Golimumab+MTX generated the highest per-person QALYs (3.75 QALY), whereas infliximab+MTX strategy generated the least QALYs (3.57). Infliximab+MTX resulted in the least direct costs of $317,455 over the patient’s life-time compared to etanercept+MTX ($324,855), adalimumab+MTX ($323,503) and golimumab+MTX ($324,159). The base-case incremental cost-effectiveness ratios (ICERs) foretanercept+MTX, adalimuamab+MTX, and golimumab+MTXcompared to infliximab+MTX were $69,211, $44,465 and $38,255/QALY, respectively. Golimumab+MTX dominated etanercept+MTX, while the ICER for golimumab+MTX vs adalimumab+MTX was $16,729/QALY. In one-way sensitivity analyses, these results were robust to a range of assumptions except for dosing of infliximab and long-term withdrawal rates. In the PSA, the probability of golimumab being cost-effective at the commonly accepted $50,000/QALY threshold was 0.29. CONCLUSIONS: Golimumab appears to be a cost-effective treatment option for RA compared to existing TNF-Is.