OBJECTIVE Two studies evaluated efficacy and safety of tanezumab versus naproxen for treatment of knee or hip osteoarthritis (OA). METHODS Randomized controlled studies [NCT00830063 (Study 1015, n=828) and NCT00863304 (Study 1018, n=840)] of subjects with hip or knee OA compared intravenous tanezumab (5 mg or 10 mg) to placebo and naproxen (500 mg twice daily). Coprimary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function (0-10 numerical rating scale), and patient's global assessment of OA at Week 16. RESULTS In both studies, tanezumab reduced pain versus placebo [least squares mean differences, 95% CI, tanezumab 5 mg: -1.21 (-1.72, -0.70); -1.13 (-1.65, -0.62); tanezumab 10 mg: -0.91 (-1.42, -0.40); -0.80 (-1.32, -0.29)], and improved function and global scores. Tanezumab 5 mg produced greater pain reduction [-0.76 (-1.28, -0.25); -0.69 (-1.21, -0.17)], and favorable functional and global outcomes versus naproxen. Pain reductions with tanezumab 10 mg versus naproxen did not reach significance, unlike functional (both studies) and global (1 study) outcomes; thus, tanezumab 10 mg was not superior to naproxen, and predefined statistical testing procedures were not met, allowing for conclusion of superiority of tanezumab 5 mg over naproxen despite replicated favorable coprimary outcomes. Tanezumab was associated with greater incidence of peripheral sensory adverse events (paresthesia, hyperesthesia, hypoesthesia, burning sensation), pain in extremity, peripheral edema, and arthralgia. Overall frequency and discontinuations as a result of adverse events were similar to placebo and naproxen. CONCLUSION Tanezumab provides efficacious treatment of knee or hip OA and may have therapeutic utility in patients with OA who experience inadequate analgesia with nonsteroidal antiinflammatory drugs.