Objective: To analyze risk factors of anastomotic leakage after McKeown'sesophagectomy. Methods: The clinical data of 635 esophageal cancer patients, who underwent McKeown's esophagectomy at Cancer Hospital of Chinese Academy of Medical Sciences from January 2012 to December 2015, were retrospectively analyzed. The risk factors of cervical anastomotic leakage were identified through analysis of medical history, surgical procedure, tumor characteristics and vascular calcification. Results: Among all the 635 patients, anastomotic leakage occurred in 111 (17.5%)patients. Univariate analysis showed that the American Society of Anesthesiologists (ASA) risk class, prior thoracic surgery, upper digestive tract ulcer, COPD, hypertension, peripheral vascular disease, renal insufficiency, FEV1% predicted, DLCO% predicted, duration of surgery and calcification of descending aorta, celiac trunk and left postceliac arteries were associated with a statistically significant increase in risk of cervical anastomotic leakage (P<0.05 for all). Logistic regression analysis showed that ASA risk class, peripheral vascular disease, renal insufficiency and calcification of descending aorta and celiac trunk were independent risk factors of cervical anastomotic leakage after McKeown's esophagectomy (P<0.05 for all). Conclusions: ASA risk class, peripheral vascular disease, renal insufficiency, calcification of descending aorta and celiac trunk are independent risk factors of cervical esophageal anastomotic leakage after McKeown's esophagectomy.