OBJECTIVE: To compare the total costs associated with two different anti-TNF agents used in the treatment of moderate to severe rheumatoid arthritis: etanercept, which can be administered at home by a subcutaneous injection, versus infliximab, which requires an intravenous infusion in day-care. METHODS: An economic model was constructed to determine the costs of both treatments. The cost evaluation included direct medical, direct non-medical and indirect costs. The perspective was that of the Dutch society. The analysis was performed for the adult RA population eligible for treatment with both agents. The base case analysis compared a monotherapy with etanercept versus a combination therapy with infliximab-MTX. Data for the economic model came from published literature, expert opinion and official price and tariff lists. RESULTS: The analysis from the society perspective showed that the total annual drug costs per patient do not differ substantially between infliximab and etanercept, with costs of NLG 31,526 (EURO 14,306) and NLG 31,334 (EURO 14,219) respectively. However the other medical costs are substantially higher for infliximab, which is due to the additional costs associated with day-care and use of MTX (NLG 12,621; EURO 5,727). Overall treatment with infliximab is more expensive than treatment with etanercept with total costs of NLG 45,115 (EURO 20,472) and NLG 31,621 (EURO 14,349), respectively (43.7% increase). The sensitivity analysis showed that the results vary with dosing and dosing interval for infliximab. CONCLUSION: Based on the assumptions used in the model, we may conclude that the use of etanercept compares favourable with infliximab: the total costs are substantially lower, while the clinical outcomes of etanercept are at least equivalent to those of infliximab.