We performed a double-blind, placebo-controlled study to evaluate the different methods of administering droperidol in patients using patient-controlled analgesia (PCA) with morphine. Eighty patients undergoing major orthopedic procedures received temazepam 0.2 mg/kg orally followed by induction of general anesthesia with propofol 2.5 mg/kg, fentanyl 2 mu g/kg, and vecuronium 0.1 mg/kg. Anesthesia was maintained with nitrous oxide, oxygen, and enflurane. At the end of surgery, all patients received PCA with morphine (0.5 mg/mL, bolus dose 1 mg, and lockout interval 5 min. Before commencement of PCA, patients were randomized to receive droperidol 1.25 mg immediately and, in addition, droperidol 0.16 mg with each PCA dose (Group 1), droperidol 1.25 mg immediately (Group 2), droperidol 0.16 mg with each PCA dose (Group 3), and no droperidol (Group 4). Incidence of nausea and vomiting, request for rescue antiemetics, sedation score, and side effects were recorded every 4 h. Droperidol significantly reduced the incidence of postoperative nausea and vomiting (PONV) (P < 0.01) and request for rescue antiemetic (P < 0.01) compared to placebo. However, there was no difference in the incidence of PONV between droperidol given either as a single dose at the end of surgery (Group 2) or mixed in morphine PCA (Group 3). The addition of droperidol in PCA after an initial dose (Group 1) should be avoided, as it resulted in more sedation and no further reduction in the incidence of PONV compared to Groups 2 and 3.