OBJECTIVES: To evaluate the changes in patient utility with treatment of active rheumatoid arthritis (RA) with leflunomide (LEF), placebo (PBO) or methotrexate (MTX). METHODS: A 52 week multicenter double-blind controlled trial comparing treatment with leflunomide, methotrexate or placebo in patients with active rheumatoid arthritis was used to derive patient utilities. Short Form 36 (SF-36) data were used to generate utility scores using the algorithm developed by Brazier et al (1999). These utilities would reflect general population values and would not be specific to an RA population. Inclusion in the utility analysis required consistent SF-36 responses, a baseline and at least one other completed assessment, and valid responses to derive the SF-6D utilities. The area under the curve was calculated for completers and the intent-to-treat population in order to estimate incremental quality adjusted life years (QALYs)for the treatments. RESULTS: The clinical study population consisted of 182 LEF, 180 MTX and 118 PBO patients. The population used for the utility analysis consisted of 165 LEF, 164 MTX and 114 (PBO). Baseline utility values were comparable between groups, ranging from 0.622 to 0.637. Incremental QALYs gained for completers was statistically significantly superior for LEF over PBO (p=0.0317) and MTX (p=0.0130). Treatment with LEF resulted in an incremental gain of 0.084 QALYs, starting from a baseline of 0.622. Similar results were seen with the intent-to-treat population. CONCLUSIONS: Treatment of RA with LEF statistically improves patient health state utility values and QALY gain over MTX and PBO.