1399 patients with symptomatic knee osteoarthritis were randomized to either topical ketoprofen 50mg, topical ketoprofen 100mg, 2.2g or 4.4g of ketoprofen-free vehicle control, oral celecoxib 100mg, or oral placebo. Patients were assessed over 12 weeks of treatment for efficacy on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and safety using the incidence of adverse events. Similar clinical efficacy over 12 weeks was noted between the 50mg and 100mg toical ketoprofen groups, ketoprofen-free vehicle control groups, and oral celecoxib group, all of which demonstrated significantly greater efficacy compared to oral placebo. GI-related adverse events were more frequent with oral intervention, while skin-related adverse events were more frequent with topical intervention.