Background Intraoperative supplemental oxygen may reduce postoperative nausea and vomiting by mitigating hypoxic stress on the gastrointestinal tract. We therefore tested the hypothesis that supplemental oxygen reduces nausea and vomiting. Methods Initially, we conducted an unplanned sub-analysis of a previous trial that evaluated the effect of 80% versus 30% intraoperative inspired oxygen on surgical site infection. Specifically, we assessed the effect of 80% versus 30% oxygen concentration on the incidence of postoperative nausea and/or vomiting. Thereafter, we conducted a systematic review and meta-analysis of the effect of supplemental oxygen on postoperative nausea and vomiting. Results The underlying trial included 2,615 patients assigned to 80% intraoperative oxygen and 2,552 patients assigned to 30% oxygen. The estimated relative risk (95% CI) of 80% versus 30% oxygen on nausea and/or vomiting was 1.03 (0.95, 1.11), P = 0.54. Furthermore, supplemental oxygen did not reduce antiemetic use or the severity of nausea and vomiting. Our meta-analysis included eleven qualifying trials (7,170 patients) and did not find a difference in postoperative nausea and vomiting: RR 0.97 [95% CI: 0.86, 1.08], P=0.55, I2=52%. Conclusions The incidence of postoperative nausea and vomiting did not differ in patients assigned to 80% or 30% inspired oxygen. A meta-analysis of available trials similarly indicated that supplemental intraoperative oxygen does not reduce postoperative nausea and vomiting. Therefore, supplemental oxygen should not be given in the expectation that it will reduce nausea and vomiting.