Cyclooxygenase-2 (COX-2) inhibitors are a class of drugs that may avoid some of the side effects of narcotics and nonsteroidal anti-inflammatory drugs (NSAIDs). We performed a randomized, double-blinded, placebo-controlled trial giving a single oral dose of the COX-2 inhibitor rofecoxib 25 mg or placebo preoperatively to determine the impact upon postoperative pain, complications, narcotic use, and hospital stay after laparoscopic cholecystectomy. Investigators and patients were blinded. Pain was measured on a 10-point visual analogue scale. Eighty patients were randomized: 40 to the rofecoxib group and 40 to the placebo group. The amount of pain between the two groups postoperatively was equivalent. Pain was recorded at 1 hour, 4.03 +/- 1.93 in the rofecoxib group versus 4.38 +/- 1.34 in the placebo group (P = 0.36); at 6 hours, 3.00 +/- 1.12 in the rofecoxib group versus 2.78 +/- 0.78 in the placebo group (P = 0.42); and at 24 hours, 1.64 +/- 0.67 in the rofecoxib group versus 2.68 +/- 1.90 in the placebo group (P = 0.17). The amount of pain medication received and lengths of hospital stay was not significantly different between the two groups. Our data demonstrate no significant benefit of preoperative oral rofecoxib in patients undergoing laparoscopic cholecystectomy.