Postoperative nausea and vomiting have been reported to be associated with the use of nitrous oxide. To further investigate this possibility, 780 patients undergoing anesthesia and surgery were randomly divided into four groups: group I: enflurane/nitrous oxide/oxygen; group II: enflurane/air/oxygen; group III: isoflurane/nitrous oxide/oxygen; and group IV: isoflurane/air/oxygen. The frequency of postoperative nausea and vomiting was ascertained in the recovery room and at 24-h follow-up by blinded observers. Other data collected included gender, age, body mass index, previous history of postoperative nausea and vomiting, and postoperative narcotic use. The authors found no association between the use of nitrous oxide and subsequent development of postoperative nausea and vomiting. Use of the 95% confidence interval allowed the authors to project a maximum potential increase in the frequency of postoperative nausea and vomiting associated with nitrous oxide to be 5.4% with enflurane and 9.7% with isoflurane in the immediate postoperative period. Female gender, younger age, and a previous history of postoperative nausea and vomiting, but not body mass index, were found to be associated with postoperative nausea and vomiting (P < 0.05). It is concluded that there is no association between the use of nitrous oxide and the development of postoperative nausea and vomiting.