The antiemetic activity of droperidol is attributed to antagonizing the dopaminergic neurons of the chemoreceptor trigger zone. Ondansetron is a serotonin (5HT) receptor antagonist at both peripheral and central 5-HT3 receptor sites with no known action on dopamine-mediated activity. We hypothesized that the combination of these two antiemetics would be more effective than droperidol alone. Women with ASA classified physical status I or II, scheduled for laparoscopic tubal banding, participated in a randomized double-blind clinical trial using a standardized anesthesia regimen. Within 15 min after induction of anesthesia, Group 1 (n = 60) received IV droperidol 1.25 mg and ondansetron 4 mg and Group 2 (n = 60) received IV droperidol 1.25 mg and saline. Before surgery and during recovery at 1, 2, and 24 h, emetic episodes, nausea, pain, drowsiness, medications taken, and adverse events were recorded. The complete response (no emesis, no rescue) for Group 1 was 55 of 60 (91.6%) versus 47 of 60 (78.3%) in Group 2 (P = 0.04). No patient needed rescue antiemetic medication in Group 1, whereas 5 of 60 (8.3%) patients were rescued in Group 2 (P = 0.03). There were seven emetic episodes in five patients in Group 1 and 30 emetic episodes in 12 patients in Group 2 over the 24-h study period (P = 0.03). The time to the first emetic episode was more than twice as long for Group 1 than Group 2 (P = 0.03) and total nausea scores were lower in Group 1 than Group 2 (P = 0.01). The droperidol/ondansetron combination was significantly superior to droperidol in complete response, time to and number of emetic episodes, and the incidence and severity of nausea in women having tubal banding.