Study objectives To compare the prophylactic antiemetic efficacy of the combination of ondansetron and droperidol with that of droperidol alone in patients undergoing elective laparoscopic cholecystectomy. Design Randomized, double-blind controlled trial. Setting University affiliated teaching hospital after induction of standardized general anesthesia. Patients 64 ASA physical status I or II patients aged 18 to 80 years, undergoing elective laparoscopic cholecystectomy. Intervention Following induction of general anesthesia, patients received either droperidol 1.25 mg intravenously (IV; n = 30; Group D) or the combination of droperidol 1.25 mg IV and ondansetron 4 mg IV (n = 34; Group D+O). Measurements Number and severity of nausea episodes, number of emetic episodes, total analgesic consumption, and rescue antiemetic administration were assessed at 1, 3, and 24 hours after admission to the recovery room. Data were analyzed using Fisher’s Exact test and unpaired Student’s t-test; a p-value <0.05 was considered significant. Results The proportions of patients who experienced nausea (70% and 53% for D and D+O groups, respectively) and vomiting (30% and 19% for D and D+O groups, respectively) were similar in the two groups. The frequency of moderate and severe nausea (requiring administration of antiemetic) was less in group D + O (7%) compared with group D (19%; p < 0.05). Conclusion Patients who received the combination of droperidol and ondansetron experienced less severe nausea compared with patients who received droperidol alone.