Objective    To investigate the risk factors for anastomotic leakage after McKeown esophagectomy, and to establish a risk prediction model for early clinical intervention. Methods    We selected 469 patients including 379 males and 90 females, with a median age of 67 (42-91) years, who underwent McKeown esophagectomy in our department from 2018 to 2019. The clinical data of the patients were analyzed. Results    Among the 469 patients, 7.0% (33/469) patients had anastomotic leakage after McKeown esophagectomy. Logistic analysis showed that the risk factors for anastomotic leakage were operation time >4.5 h, postoperative low albumin and postoperative hypoxemia (P<0.05). A prognostic nomogram model was established based on these factors with the area under the receiver operator characteristic curve of 0.769 (95%CI 0.677-0.861), indicating a good predictive value. Conclusion    Operation time >4.5 h, postoperative low albumin and postoperative hypoxemia are the independent risk factors for anastomotic leakage after McKeown esophagectomy. Through the nomogram prediction model, early detection and intervention can be achieved, and the hospital stay can be shortened.