A gender difference in the incidence of acute pain may be a confounder in analgesic trials. We have tested the hypothesis that the incidence of acute pain after knee arthroscopic procedures is greater in women than men. We performed three RCTs on intra-articular analgesics in which no postoperative analgesia was given until the need for such treatment was documented by scoring moderate-to-severe pain on a verbal rating scale (VRS 0-4; n=219), and a 0-100 mm visual analogue pain scale (VAS) within 2 h postoperatively. All trials were performed with an intra-articular catheter technique. The design allowed us to study the natural course of pain after arthroscopic surgery until analgesia was required. Women reported more pain of at least moderate intensity than men (84 vs 57%; P<0.0001), indicating that being female is a risk factor for early postoperative pain (RR 1.47, 95% confidence interval from 1.23 to 1.74). The VAS score corresponding to moderate and severe pain is similar in men and women. Only short acting anaesthetics were given in order to minimise carry-over effects. Since previous trials on arthroscopic analgesics neither measured baseline pain nor stratified for gender, a difference between treatment groups could result from an uneven distribution regarding these factors. Our findings have major implications for the interpretation of previously published trials on intra-articular analgesia.