OBJECTIVE: To compare the cost-effectiveness of valdecoxib 20 mg once daily (qd) and diclofenac 75 mg slow release (SR) twice daily (bid) in the treatment of RA based on prospectively collected data of healthcare resource utilization in a randomized controlled trial (RCT, study 062) over 6 months. The cost-effectiveness evaluations were calculated for the UK from a National Health Service payer perspective, and for Germany from a Sickness funds payer perspective. METHODS: Study 062 compared efficacy and safety of valdecoxib 20 mg qd (n=246) with diclofenac 75 mg SR bid (n=237) in adult patients with RA. The cost-effectiveness of valdecoxib and diclofenac was compared using country-specific unit costs for resource use (hospital days, medications, unscheduled procedures and health care visits) in the UK and Germany. The cost-effectiveness ratios were calculated for cost/averted gastroduodenal (GD) ulcer, cost/averted withdrawal due to treatment failure and/or adverse event, cost/averted gastrointestinal (GI) serious adverse event (SAE), and cost/avoided ulcer with GI SAE. RESULTS: The study showed comparable efficacy and a superior safety profile for valdecoxib, resulting in fewer GI adverse events and hospital days. The cost/averted GD ulcer in the UK was -£1104 and 386€ in Germany. The cost/averted withdrawal due to treatment failure and/or adverse event was -£1580 in the UK and 553€ in Germany. The cost/averted GI SAE was -£2709 in the UK and 947€ in Germany, and the cost/avoided ulcer with GI SAE was -£3522 in the UK and 1436€ in Germany. CONCLUSIONS: The superior safety profile of valdecoxib compared with diclofenac translates into lower total health care costs for patients treated with valdecoxib, and overall cost effectiveness in both countries.