Background: This study was designed to compare the antiemetic effects of propofol, ondansetron, droperidol and metoclopramide for the prevention of postoperative nausea and vomiting (PONV) in patients undergoing middle ear surgery. Methods: One-hundred-twenty patients were scheduled for middle ear surgery (tympanomastoidectomy and tympanoplasty). Patients received propofol (0.5 mg/kg), ondansetron (60㎍/kg), droperidol (20㎍/kg) or metoclopramide (0.2 mg/kg) intravenously at the end of the surgical procedure. The assesment of PONV was performed during 3 periods after receiving anesthesia; 0 to 2 hours in the postanesthetic care unit, 2 to 12 hours and 12 to 24 hours in the ward. Results: The percentage of no emesis during the 0 to 2 hour period after receiving anesthesia was 93% for the those who received propofol, 73% for the those who received ondansetron, 70% for the those who received droperidol, and 70% for the those who received metoclopramide. The respective corresponding incidence during the 2 to 12 hour period after receiving anesthesia was 86%, 66%, 63%, and 63%, and the respective corresponding incidence during the 12-24 hour period after receiving anesthesia was 90%, 66%, 66%, and 66%. No clinically adverse events were observed in any of the groups. Conclusions: A small dose of propofol is a better antiemetic than ondansetron, droperidol or metoclopramide for prevention of postoperative nausea and vomiting after middle ear surgery. (Korean J Anesthesiol 2202; 42: 468~473)