Fifty patients with acute ankle sprains/strains were treated with either 100 mg flurbiprofen or 500 mg diflunisal twice daily in a double-blind fashion for 18 days or until symptoms of the injury resolved. Tolerability of the drugs was evaluated by recording the occurrence of adverse drug reactions and monitoring laboratory parameters. Efficacy measurements were performed at enrollment and at Visit 2-Day 7, Visit 3-Day 14 and Visit 4-Day 21 to determine relief of symptoms and return to normal activities. Patients in both treatment groups exhibited marked improvement by Visit 2-Day 7 with almost complete recovery by Visit 3-Day 14. Flurbiprofen patients had a significantly shorter duration of therapy. Results from three of the six physician assessments were marginally to significantly superior for patients in the flurbiprofen group. The only reported adverse event was mild gastro-intestinal intolerance in a patient receiving diflunisal. Flurbiprofen and diflunisal appear to be effective and well-tolerated medications for the treatment of acute ankle sprains and strains.