The efficacy, tolerability, and acceptability of topical applications of ketoprofen gel (2.5% w/w), piroxicam gel (0.5% w/w), and diclofenac gel (1% w/w), when administered three times daily for 5 days, in the treatment of acute (within 48 hours) soft-tissue injury, were compared in an open-label, randomized, multicenter, general practice study. Of 1575 patients recruited, 1048 received ketoprofen gel (525 used the gel with a dose-measuring device), 263 received piroxicam gel, and 264 received diclofenac gel. Ketoprofen gel was significantly superior to piroxicam gel in terms of global assessment of treatment response (improvement in 74% vs 65% of patients) and the severity of the injury (38% vs 26% "greatly improved") and in improvements in stiffness (71% vs 64%), restriction of mobility (34% vs 22%), and pain on pressure (81% vs 78%) and movement (83% vs 77%). Ketoprofen gel also compared favorably with diclofenac gel, with a larger proportion of patients assessing a great improvement in the injury (38% vs 30%). Patient acceptability of ketoprofen gel was significantly better than piroxicam gel. More patients noted a significant cooling effect with ketoprofen gel (71%) than with either piroxicam gel (49%) or diclofenac gel (60%). Ketoprofen gel also showed excellent tolerability. In conclusion, ketoprofen gel may offer benefits over established therapies for the treatment of acute soft-tissue injury.