BACKGROUND: This study was designed to establish the optimal timing of administration of ondansetron for prevention of postoperative nausea and vomiting (PONV) during intravenous patient-controlled analgesia (IV-PCA). METHODS: Eighty women undergoing a total abdominal hysterectomy under general anesthesia were randomized to receive a placebo (n = 20, group 1), ondansetron 2 mg before induction and 2 mg after surgery (n = 20, group 2), ondansetron 4 mg before induction (n = 20, group 3), or ondansetron 4 mg after surgery (n = 20, group 4). An IV-PCA using butorphanol and ketorolac was connected to the patients after waking from the anesthesia. The incidences and severity of nausea and vomiting were recorded for 48 hr postop. RESULTS: The incidences of nausea and vomiting in group 1 (75%, 40%) were significantly decreased after ondansetron administration but there were no significant differences among the ondansetron groups (group 2; 45%, 20%, group 3; 45%, 15%, group 4; 40%, 10%) (P < 0.05). CONCLUSIONS: The prophylactic administration of ondansetron is effective in preventing PONV during IV-PCA, but the timing of ondansetron administration has no effect on its efficacy.