A randomized, single-blind, parallel study involving 100 adults was performed to compare the efficacy and safety of naproxen sodium with that of pirprofen in the treatment of moderate to severe pain after orthopaedic surgery. Fifty patients received 550 mg of naproxen sodium initially and 275 mg every 6 h thereafter, and 50 received 400 mg of pirprofen every 8 h until either their pain was completely relieved or the 3-day trial ended. Patients who required additional analgesia were given 500 mg of paracetamol 2 h after administration of the test medication. Both medications significantly relieved post-operative pain, and there were no statistically significant differences in efficacy between the groups. Six patients receiving naproxen sodium and two patients receiving pirprofen withdrew from the study because of lack of efficacy. Thirteen patients receiving naproxen sodium recorded 17 adverse events and 13 patients receiving pirprofen recorded 20 adverse events, again with no statistically significant differences between groups. Six patients in each group withdrew from the study because of these adverse events. Naproxen sodium and pirprofen were equally safe and effective in relieving post-operative pain following musculoskeletal surgery.