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Xu Lin,1,* Pei Wang,1 Ding-Wei Liu,2 Yu-Wei Guo,1 Chun-Hui Xie,3 Bin Wang,1,* Rui Dong,4 Li-Xin Sun,1 Ming-Shan Wang,1 Yan-Lin Bi1 1Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 2Department of Laboratory, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 3Department of Anesthesiology, Weifang Medical University, Weifang, People’s Republic of China; 4Department of Anesthesiology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Lin Bi; Ming-Shan WangDepartment of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of ChinaTel +86 186 6167 5610; +86 186 61675608Email yanlinbi68@sina.cn; wmsqingdao@163.comPurpose: Postoperative delirium (POD) is common in elderly patients undergoing laparoscopic surgery for gastric and colorectal malignancies. POD may be affected by different fraction of inspired oxygen (FiO2). The purpose of this study was to compare the effects of different FiO2 on POD.Patients and Methods: A randomized, double-blind controlled trial was performed in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 662 patients aged 65 to 85 years old underwent isolated laparoscopic radical gastrectomy, radical resection of colon cancer, or radical resection of rectal cancer only. A random number table method was used to divide the patients into two groups: 40% FiO2 (group A) and 80% FiO2 (group B). The primary endpoint was the incidence of POD, which was assessed by the Confusion Assessment Method (CAM) twice daily during the first 7 postoperative days, and POD severity was measured by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the intraoperative regional cerebral oxygen saturation (rSO2), Bispectral (BIS) index, invasive arterial blood pressure (IABP), oxygen saturation (SpO2), end-tidal carbon dioxide partial pressure (PETCO2), the number of atelectasis cases and visual analogue scale (VAS) scores on days 1– 7 after surgery.Results: The incidence of POD was 19.37% (122/630), including 20.38% (64/314) in group A and 18.35% (58/316) in group B. No statistical significance was found in the incidence of POD between the two groups (P > 0.05); compared with group B, SpO2, rSO2 and PaO2 decreased at T2 to T4 time point (P < 0.01), and the incidence of postoperative atelectasis decreased (P < 0.05) in group A.Conclusion: The incidence of POD was not significantly affected by different FiO2 and the incidence of postoperative atelectasis was decreased at low FiO2.Keywords: intraoperative oxygen concentration, postoperative delirium, malignancy