Baokground: Patients with perioperative bleeding during cardiac surgery are susceptible to acute kidney injury (AKI) which is proposed to be associated with short-term and long-term risk of adverse events. The relationship between perioperative bleeding in off-pump coronary artery bypass grafting (OPCAB) and AKI remains unknown. The purpose of this study is to evaluate the impact of perioperative bleeding on the risk of postoperative AKI in patient undergoing OPCAB. Methods: Perioperative major bleeding was defined by the universal definition of perioperative bleeding (UDPB) class 3 to 4. The primary endpoint was postoperative AKI which was diagnosed using criteria of stage 1 of AKI proposed by Acute Kidney Injury Network (AKIN). The secondary endpoints included inhospital mortality and the incidence of postoperative myocardial infarction (MI). Baseline characteristics were compared between patients with and without major bleeding. Multivariable logistic regression analysis was performed to identify potential predictive factors for AKI after OPCAB. Results: A total of 4,030 ACS (acute coronary syndrome) patients who underwent OPCAB were included in this study. Major bleeding rate was 9.8% (n =394). AKI was found in 995 (24.7%) patients. Multivariable regression analysis showed that perioperative major bleeding conferred a significantly higher risk of AK I after OPCAB with an odds ratio of 1.67 (95% confidence interval 1.32-2.10, P<0.001). When a decrease in hemoglobin, transfusion and chest tube output were included in the same logistic model separately to replace major bleeding, transfusion was the most strongly risk factor associated with AKI after surgery (OR =2.08, 95% CI: 1.38-3.16, P<0.001). Conclusions: Perioperative bleeding is associated with a higher risk of postoperative AKI in ACS patients who underwent OPCAB. Moreover, blood and bk)od products transfusion most correlated with AKI after surgery. Prevention of severe bleeding and reducing blood transfusion requirement may improve the outcomes of OPCAB.