Current treatments for post-injury movement-evoked pain are inadequate. Non-opioids may complement opioids, which preferentially reduce spontaneous pain, but most have incomplete efficacy as single agents. This trial evaluates efficacy of a gabapentin-rofecoxib combination following hysterectomy. In addition to IV-PCA morphine, 110 patients received either placebo, gabapentin (1800 mg/day), rofecoxib (50 mg/day) or a gabapentin-rofecoxib combination (1800/50 mg/day) starting 1 h pre-operatively for 72 h. Outcomes included pain at rest, evoked by sitting, peak expiration and cough, morphine consumption and peak expiratory flow (PEF). For placebo, gabapentin, rofecoxib and combination, 24 h pain (100 mm VAS) was: at rest-23.6 (P<0.05 vs. all treatments), 13.8, 14.4 and 12.1; during cough-50.7 (P<0.05 vs. all treatments), 41.5, 44.8 and 30.8; 48 h morphine consumption (mg) was: 130.4 (P<0.05 vs. all treatments), 81.7, 75.6 and 57.2 (P<0.05 vs. gabapentin and rofecoxib) and 48 h PEF (% baseline) was: 63.9 (P<0.05 vs. all treatments), 77.2, 76.7 and 87.5 (P<0.05 vs. gabapentin and rofecoxib). Adverse effects were similar in all groups except sedation which was more frequent with gabapentin. Combination and rofecoxib reduced pain interference with movement, mood and sleep (P<0.05) and combination was superior to gabapentin for all these three (P<0.05). These data suggest that a gabapentin-rofecoxib combination is superior to either single agent for postoperative pain. Other benefits include opioid sparing, reduced interference with movement, mood and sleep and increased PEF suggesting accelerated pulmonary recovery. Future research should identify optimal dose-ratios for this and other analgesic combinations.