82 patients with symptomatic knee osteoarthritis were randomized to receive either acetaminophen, diclofenac, or placebo for 12 weeks. Patients were assessed on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Lequesne Index, and safety over 12 weeks of treatment. Within-group reduction in WOMAC scales from baseline was only significant in the diclofenac group. Between-group comparisons demonstrated significant differences between diclofenac and acetaminophen, and diclofenac and placebo, regarding the effect on WOMAC scales.