918 patients (>=40 yr) with osteoarthritis (OA) of the knee and managed with oral NSAIDs or acetaminophen, were randomized to 4 groups of either naproxcinod (750 or 375 mg), naproxen (50 mg) or a placebo. At study conclusion (i.e. 13 weeks), naproxcinod was found to be well-tolerated and did not significantly elevate blood pressure more than naproxen. Naproxcinod's clinical efficacy is statistically superior to placebo for symptom control of knee OA, and the 750 mg dosage was significantly non-inferior to naproxen 500 mg for pain, function and the patient's overall rating of disease status.