Objective    To analyze the risk factors of anastomotic leakage after esophagectomy. Methods    The clinical data of 1 328 patients with esophageal cancer, who underwent esophagectomy in the First Affiliated Hospital of Henan University of Science and Technology from January 2010 to December 2016, were retrospectively analyzed. There were 726 males and 602 females, at an average age of 67.2±14.1 years. According to whether there was anastomotic leakage after operation, patients were divided into two groups: an anastomotic leakage group (167 patients) and a non-anastomotic leakage group (1 161 patients). Univariate and multivariate logistic regression analysis was used to identify related risk factors of anastomotic leakage after operation. Results     The incidence of postoperative anastomotic leakage was 12.6% (167/1 328). Univariate analysis showed that body mass index, arrhythmia, chronic obstructive pulmonary disease (COPD), diabetes, preoperative albumin level, preoperative chemotherapy and chemoradiotherapy, lesion location, anastomosis types and postoperative pulmonary infection were associated with statistically significant increase in risk of cervical anastomotic leakage (P<0.05). Logistic regression analysis showed that preoperative COPD, lesion location and postoperative pulmonary infection were independent risk factors of cervical anastomotic leakage after esophagectomy (P<0.05). Conclusion    The occurrence of cervical anastomotic leakage after esophageal cancer is related to many factors. The preoperative COPD, the lesion location and the postoperative pulmonary infection are independent high risk factors. Paying attention to these factors and doing perioperative management can effectively reduce the occurrence of anastomotic leakage.