Ankle sprains are common acute soft-tissue injuries. This 7-day open-label, multicentre, randomized study compared the efficacy and safety of celecoxib with non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in treating acute ankle sprain with moderate-to-severe ankle pain in 278 patients. Patients received either celecoxib (400 mg loading dose followed by 200 mg twice daily) or standard doses of non-selective NSAIDs. The primary endpoint was a change in the patient's assessment of ankle pain on a 0 mm (no pain) - 100 mm (worst possible pain) visual analogue scale (VAS) at day 3 compared with baseline. From a baseline of 73 mm, mean VAS pain scores decreased to 29 and 32 mm in the celecoxib and non-selective NSAID groups, respectively. The lower limit of the 95% confidence interval for the treatment difference with regard to change from baseline was greater than the pre-established non-inferiority margin of -10 mm. Using an initial loading dose, celecoxib was at least as efficacious as non-selective NSAIDs in treating acute pain due to ankle sprain.