BACKGROUND Laparoscopic cholecystectomy is associated with shorter hospital stay and less pain in comparison to open surgery. The aim of this study was to evaluate the effect of intraperitoneal hydrocortisone on pain relief following laparoscopic cholecystectomy. METHODS Sixty two patients were enrolled in a double-blind, randomized clinical trial. Patients randomly received intraperitoneal instillation of either 250 ml normal saline (n=31) or 100 mg hydrocortisone in 250 ml normal saline (n=31) before insufflation of CO2 into the peritoneum. Abdominal and shoulder pain were evaluated using VAS after surgery and at 6, 12, and 24 hours postoperatively. The patients were also followed for postoperative analgesic requirements, nausea and vomiting, and return of bowel function. RESULTS Sixty patients completed the study. Patients in the hydrocortisone group had significantly lower abdominal and shoulder pain scores (10.95 vs 12.95; P<0.01). The patients were similar regarding analgesic requirements in the recovery room. However, those in the hydrocortisone group required less meperidine than the saline group (151.66 (±49.9) mg vs 61.66 (±38.69) mg; P=0.00). The patients were similar with respect to return of bowel function, nausea and vomiting. No adverse reaction was observed in either group. CONCLUSIONS Intraperitoneal administration of hydrocortisone can significantly decrease pain and analgesic requirements after laparoscopic cholecystectomy with no adverse effects.