The efficacy and tolerability of etodolac and indomethacin were compared in patients with osteoarthritis of the knee. Sixty-four patients entered a double-blind, parallel trial and were randomly assigned to receive 300 mg etodolac twice daily (n = 31) or 50 mg indomethacin 3-times daily (n = 33) for 6 weeks. Both groups showed significant (p less-than-or-equal-to 0.05) improvement from baseline in all efficacy assessments at the final evaluation. However, significantly (p less-than-or-equal-to 0.05) greater decreases from baseline were seen for etodolac than for indomethacin in patients' global evaluation, pain intensity, night pain, standing pain, walking pain, pain getting up from a chair, tenderness on pressure, and knee flexion. In addition, 67% of the patients in the etodolac group indicated improvement in their condition at the final evaluation, compared with 53% of the patients who received indomethacin. No patients in the etodolac group withdrew because of adverse reactions compared to 4 patients in the indomethacin group. Furthermore, significantly more patients in the indomethacin group (52%) than in the etodolac group (19%) reported drug-related adverse reactions. Thus, the results of this study strongly indicate that etodolac is more effective and produces fewer side-effects than indomethacin in the treatment of patients with osteoarthritis.