This study compared the efficacy and safety of etodolac, a new nonsteroidal anti-inflammatory drug of the pyranocarboxylic class, with that of diclofenac in patients with osteoarthritis of the knee. A total of 172 patients entered this double-blind, parallel study and were randomly assigned to receive etodolac 600 mg/day (n = 85) or diclofenac 150 mg/day (n = 87) for 8 weeks. Both treatment groups showed a statistically significant reduction in pain at the second week and significant improvement (P < or = 0.05) from baseline in all efficacy assessments for the remainder of the study. Seventeen (20%) patients in the etodolac group and 21 (24%) patients in the diclofenac group reported at least one adverse event. Seven (8%) patients treated with etodolac and eight (9%) of those receiving diclofenac withdrew prematurely from the trial. One diclofenac-treated patient had a significant increase in alanine aminotransferase at the final evaluation. The results of this study indicate that etodolac was well tolerated and as effective as diclofenac in relieving the signs and symptoms of osteoarthritis.