Study Objective To assess the efficacy of intraoperative inspired oxygen fractions (FIO 2) of 0.8 and 0.5 when compared with standard FIO 2 of 0.3 in the prevention of postoperative nausea and vomiting (PONV). Design Prospective, randomized, double-blinded, controlled study. Setting General hospital, postanesthesia care unit (PACU), and gynecology floor room. Patients 120 ASA physical status I and II women, aged 21 to 76 years, undergoing elective gynecologic laparoscopic surgery. Interventions Patients were randomized to receive a gas mixture of 30% oxygen in air (FIO 2 = 0.3, Group G30), 50% oxygen in air (FIO 2 = 0.5, Group G50), or 80% oxygen in air (FIO 2 = 0.8, Group G80); there were 36 patients in each group. A standardized sevoflurane general anesthesia, postoperative pain management, and antiemetic regimen were used. Measurements Frequency of nausea, vomiting, and both was assessed for early (0 to two hrs) and late PONV (two to 24 hrs), along with use of rescue antiemetic, degree of nausea, and severity of pain. Main Results There was no overall difference in the frequency of PONV at the early and late assessment periods among the three groups. G80 patients had significantly less vomiting than Group G30 at two hours, 3% (1/36) vs. 22% (8/36), respectively, P = 0.028. Nausea scores, rescue antiemetic use, pain scores, and opioid consumption did not differ among the groups. Conclusion High intraoperative FIO 2 of 0.8 and FIO 2 of 0.5 do not prevent PONV in patients without antiemetic prophylaxis. An intraoperative FIO 2 of 0.8 has a beneficial effect on early vomiting only.