Purpose <p>Intraoperative supplemental oxygen may induce postoperative organ complications by aggravating oxidative stress and vasoconstriction. This meta-analysis was to determine whether the higher fraction of inspired oxygen (FiO₂) would increase the risk of organ complications among patients under general anesthesia.</p> Methods <p>We performed a systematic literature review for randomized controlled studies among surgical patients receiving ≥ 60% FiO₂ compared with ≤ 40% FiO₂ and meta-analysis of risk ratios (RR) comparing higher FiO₂ against lower for pulmonary, cardiac, neurological, and kidney complications. We systematically explored MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials to December 2024.</p> Results <p>We included 20 qualifying randomized controlled trials with a total of 5,793 patients. Low FiO₂ was associated with less atelectasis (RR, 0.78; 95% CI, 0.63–0.97), lower percentage of atelectasis (mean difference, –1.80; 95% CI, –3.30 to –0.57), and more acute kidney injury (RR, 1.64; 95% CI, 1.15–2.34). No evidence of association with low FiO₂ was found for other complications in this meta-analysis: cardiac complications (RR, 1.15; 95% CI, 0.96–1.53) and delirium (RR, 1.13; 95% CI, 0.87–1.46).</p> Conclusions <p>The current study indicated that lower intraoperative oxygen reduced postoperative incidence and severity of atelectasis but result in more acute kidney injury. More high-quality trials are warranted regarding the optimal fraction of intraoperative inspired oxygen.</p> Registration <p>Prospectively registered at the International Prospective Registry of Systemic Reviews (CRD42023479131).</p>