OBJECTIVES: To compare the improvement of hip and knee osteoarthritis during treatment with naproxen. METHODS: Men and women aged 40 to 75 years with symptomatic osteoarthritis of the knee or hip of at least three months' duration participated in a six week placebo controlled, double blind study with naproxen 500 mg twice daily as one treatment arm. Naproxen was given to 403 patients (280 knee, 123 hip) and placebo to 108 patients (75 knee, 33 hip). WOMAC (Western Ontario and McMaster Universities osteoarthritis index) 3.1 visual analogue scale and SF-36 (36 item short form health survey) were used to assess response to treatment between baseline and week 6. RESULTS: There were no differences at baseline between knee and hip osteoarthritis for any of the WOMAC subscales or SF-36 domains. Improvement was between 4 and 7 mm greater for knee than for hip for all WOMAC subscales (pain, delta = 4.7 mm (p = 0.03); stiffness, delta = 6.6 mm (p = 0.004); function, delta = 4.8 mm (p = 0.06)). Effect size was about 0.8 for all WOMAC subscales for the knee and between 0.5 and 0.6 for the hip. Knee patients treated with naproxen improved 4.6 (p = 0.033) more than hip patients for SF-36 bodily pain and 10.3 (p = 0.014) more for SF-36 role-physical. CONCLUSIONS: Patients with knee osteoarthritis improved more with naproxen treatment than patients with hip osteoarthritis, as monitored by WOMAC and the SF-36 domains bodily pain and role-physical. These findings warrant further investigation and strongly suggest that efficacy of treatment of osteoarthritis of knee and hip should be evaluated separately.