OBJECTIVE: Adalimumab is a new human TNF-antagonist monoclonal antibody used to treat patients with moderate to severe RA. We used an economic model to compare its cost effectiveness to other biologic disease modifying anti-rheumatic drugs (DMARDs) such as etanercept and infliximab. METHODS: Adhering to the US cost-effectiveness panel and AMCP guidance, the model evaluated adalimumab with methotrexate (MTX) as it would be given in typical practice. The analysis was performed over 3 years from a payor's perspective and is based on individual simulation of 10,000 RA patients. Patients' clinical responses were evaluated every six months. Probabilities were derived from clinical (Phase III ARMADA trial) and long-term observational databases. Costs included the drug, monitoring, administration, RA-related hospitalization and treatment of adverse events. Comprehensive sensitivity analyses were performed to highlight key uncertainties. RESULTS: Using ACR50 clinical response data, adalimumab + MTX resulted in a more sustained response with a lower cost-effectiveness ratio compared to etanercept + MTX and with infliximab + MTX. Adalimumab data entered into the 3-year model yielded findings that patients had 1.36 years of good clinical response and a cost-effectiveness ratio of $45,600 per year of response. Results for etanercept + MTX were 1.16 years and $53,900, while results for infliximab + MTX were 0.69 years and $95,600. Sensitivity analysis on clinical response confidence intervals (CIs) revealed that cost-effectiveness of the biologics overlapped, however CIs for adalimumab were narrower because of larger trial sample sizes. CONCLUSION: Uncertainty in comparative efficacy is currently too large to definitively prove that one biologic DMARD is always more cost-effective than the others, but larger sample sizes in adalimumab trials give higher certainty regarding its efficacy. Since formulary decisions are made on data currently available, these results suggest that adalimumab + MTX is as cost effective and possibly more cost effective than the other biologic DMARDs.