Background: Nausea and vomiting are the most common causes of postoperative complications, and they are seen most often after operations performed using general anesthesia and sedation. We designed this study to compare the effects of droperidol, metoclopramide, tropisetron, and ondansetron for the prevention of postoperative nausea and vomiting in patients undergoing gynecologic operations. Methods: One hundred patients were randomly assigned to 1 of 5 groups: group D was given 2.5 mg droperidol; group M, 10 mg metoclopramide; group T, 2.5 mg tropisetron; group O, 4 mg ondansetron 5 min after induction, and group C was the control group and received no prophylactic antiemetic treatment. All patients were observed for sedation and postoperative nausea and vomiting for 48 h. Results: Within 24 h after the operation, severe postoperative nausea and vomiting were seen in 4 patients (20%) in group D, 8 (40%) in group M, 5 (25%) in group T, 3 (15%) in group O, and 12 patients (60%) in the control group. Patients receiving droperidol, tropisetron, and ondansetron had significantly less serious emesis than the control group (p < 0.05). Sedation was seen in 5 patients receiving droperidol (4 patients score 2; and 1 patient score 3) and tropisetron (2 patients score 2; and 3 patients score 3) 15 min after surgery; this was significantly higher than in the control group (p < 0.05). Conclusion: We conclude that metoclopramide is not effective in preventing postoperative nausea and vomiting after gynecologic operations. Droperidol, tropisetron, and ondansetron are effective; however, the sedating effects of droperidol and tropisetron should be considered.