Interim results are reported for three double-blind clinical trials comparing etodolac, a new nonsteroidal anti-inflammatory drug (NSAID), with piroxicam, diclofenac, or naproxen in patients with osteoarthritis (OA) of the knee. Patients assigned to receive etodolac were given 200 mg three times a day in the diclofenac comparison and 300 mg twice a day in the other two studies. The comparator groups in the three studies received piroxicam 20 mg once a day, diclofenac 50 mg three times a day, or naproxen 500 mg twice a day. The length of the studies ranged from 6 to 12 weeks, and patients were seen at baseline and every 2 weeks thereafter. Etodolac, piroxicam, and diclofenac treatment consistently resulted in similar and statistically significant changes from baseline, indicative of improvement, in all primary efficacy variables (physicians' and patients' global assessments of improvement, pain intensity, and night pain) at every evaluation. In the comparison with naproxen, patients who received etodolac showed statistically significant improvement at most evaluations, whereas significant changes were less frequent in the naproxen group. Response rates in the three studies (response was defined as a decrease of 1 or more units in the patient's overall global evaluation, which is based on a 5-point scale ranging from 1 = very good to 5 = very poor) were as follows: etodolac 72%, piroxicam 75%; etodolac 66%, diclofenac 56%; and etodolac 40%, naproxen 16%. These interim results suggest that the efficacy of etodolac compares favorably with that of other NSAIDs in the treatment of OA of the knee.