The prophylactic antiemetic efficacy of intravenous (i.v.) ondansetron, droperidol, perphenazine, and metoclopramide was evaluated in a prospective, double-blind study of 360 ASA physical status I-III patients undergoing total abdominal hysterectomy (TAH). Subjects were randomized to receive i.v., one of ondansetron 4 mg, droperidol 1.25 mg, perphenazine 5 mg, metoclopramide 10 mg, or placebo prior to induction of anesthesia. Hypotension immediately after administration of metoclopramide was observed in two patients and four patients given ondansetron developed profound systolic hypotension at induction of anesthesia. Twenty-two percent of patients receiving droperidol became sedated. Postoperatively, patients developing severe nausea, retching, or vomiting, defined as severe emetic sequelae (SES), were deemed to have failed antiemetic prophylaxis and received antiemetic rescue. A significantly larger number of patients who received i.v. ondansetron (63%), droperidol (76%), and perphenazine (70%) were free of SES when compared to placebo (43%); P < 0.05. Metoclopramide was ineffective. Although ondansetron, droperidol, and perphenazine were effective in providing antiemetic prophylaxis, only i.v. perphenazine was free of side effects. Hence, we conclude that perphenazine is the best choice for antiemetic prophylaxis after TAH.