An open comparative study was carried out to evaluate the efficacy and safety of piroxicam FDDF, for sublingual administration, versus naproxen in the treatment of osteoarthritis. Sixty-one patients with acute-phase osteoarthritis involving various joints are reported. They were treated with 20 mg/day piroxicam FDDF or with 1000 mg/day naproxen for a total of 4 weeks. Drug efficacy was evaluated on the base of the variation of spontaneous pain, pain on motion, functional limitation and capacity to perform a specific activity. The intensity of spontaneous pain on the first day showed a statistically significant improvement with both drugs, but the onset of analgesia was only after 15 minutes with piroxicam and after 1 hour with naproxen. The improvement in pain intensity increased on the first day and until the 7th day with both drugs, but the comparative analysis between the analgesic efficacy of the two treatments proved to be favourable to piroxicam. On the 7th day, pain on motion and the capacity to perform a specific activity showed a statistically significant improvement with both drugs, but the comparative analysis between the two treatments proved to be favourable to piroxicam. The two drugs showed the same efficacy in functional restriction. The local and systemic tolerability of piroxicam was good. Only 5 patients experienced 6 systemic side-effects, and 1 patients showed local side-effects, but 11 patients of the naproxen group showed 12 systemic side-effects. Thus piroxicam showed a better analgesic and anti-inflammatory efficacy than naproxen. Piroxicam proved to have a better systemic tolerability than naproxen. The local tolerability of piroxicam FDDF was good.