BACKGROUND: Patients with acute lung injury who received lower tidal volume (VT) ventilation had significantly fewer days with acute kidney injury (AKI) when compared to those receiving higher VTs. There is a paucity of studies on the relationship between intraoperative VTs and postoperative AKI in patients undergoing noncardiac surgery. We therefore sought to assess the association of mean delivered intraoperative VT per kilogram based on predicted body weight (PBW) and postoperative AKI. METHODS: This retrospective cohort study was conducted in a large tertiary multispecialty academic medical center. Adult patients who underwent noncardiac surgery between January 2005 and July 2016 under general anesthesia with endotracheal intubation and mechanical ventilation were included. A total of 41,224 patients were included in the study. The relationship between mean intraoperative VT per PBW and AKI was assessed using logistic regression, adjusting for prespecified potential confounding variables. The secondary outcomes were postoperative major pulmonary complications, myocardial injury after noncardiac surgery (MINS), and in-hospital mortality. RESULTS: The incidence of AKI was 10.9% in the study population. Postoperative renal replacement therapy was required in 0.1% of patients. Higher delivered mean intraoperative VT per PBW was significantly associated with increased odds of AKI. The estimated odds ratio for each 1 mL increase in VT per kilogram of PBW (1 unit) was 1.05 (95% confidence interval [CI], 1.02–1.08; P = .001), after adjusting for potential confounding variables. A higher delivered mean intraoperative VT per PBW was significantly associated with increased odds of postoperative myocardial injury and was not significantly associated with major postoperative pulmonary complications or in-hospital mortality after noncardiac surgery. CONCLUSIONS: In adult patients undergoing noncardiac surgery, higher delivered mean intraoperative VTs per PBW are associated with an increased odds of developing AKI.