BACKGROUND: This study was designed to compare the efficacy and safety of ondansetron with droperidol in the prevention of postoperative nausea and vomiting (PONV) using intravenous patient-controlled analgesia (IV-PCA). METHODS: Sixty women were randomly allocated to one of four groups after total abdominal hysterectomy under general anesthesia, droperidol 1 mg (Group 1), 2 mg (Group 2), ondansetron 2 mg (Group 3), 4 mg (Group 4) bolus injection with butorphanol 1 mg and added the same drug to PCA drug (butorphanol 10 mg). The severity of pain, nausea, vomiting and sedation were assessed at 0, 1, 2, 6, 12, 24, 36 and 48hr postoperatively. RESULTS: The occurrence of nausea and vomiting was significantly higher in Group 1, 2 than Group 4. The sedation score and incidence of dizziness were significantly higher in Group 1, 2 than Group 3, 4. CONCLUSIONS: The addition of ondansetron to PCA drug is more effective and safe in the prevention of postoperative nausea and vomiting and has less sedation and dizziness effect than droperidol. But, droperidol has a cost-saving effect.