Background: Post-esophagectomy airway fistula (PEAF) is a serious complication after esophageal cancer resection. At present, the clinical characteristics, treatments and prognosis of PEAF patients remain inconclusive. We aimed to investigate these problems of patients with PEAF through a multi-center retrospective cohort study. Methods: We included consecutive patients who underwent esophagectomy for esophageal cancer in seven major Chinese esophageal cancer centers from January 2010 to December 2020. Based on the anatomic characteristics of PEAF patients, PEAFs were divided into Union type I (without digestive fistula) and Union type II [respiratory-digestive fistula (RDF)], and subtypes a and b (tracheal or bronchial fistulas), as well as L1 and L2 (same or different level of fistulas). The clinical characteristics, diagnoses, managements, and effects of the various types were retrospectively analyzed. Results: PEAF occurred in 85 of 26,608 patients (0.32%), including eight females and 77 males. There were 16 patients with type I and 69 with type II. The numbers of healings, non-healings, and deaths at discharge were 45 (52.9%), 20 (23.5%), and 20 (23.5%), respectively. Type Ib was common in type I, and type II L1 was common in type II. The healing rates of surgical, stent, and conservative treatments were 50%, 60%, and 50%, respectively. All type I patients treated with stent implantation were healed at discharge. The healing rates, mortality, and 3-year survival of type II L1 and type II L2 patients were 55.4% and 30.8%, 17.9% and 30.8%, and 34.3% and 15.4%, respectively. The 5-year survival rates of all PEAFs were 21.1%. Conclusions: PEAF is an infrequent and life-threatening complication after esophagectomy. Patients with different types of PEAF often have different inducements. In this study, we found that the healing rates of surgical and conservative treatments were similar, and stent implantation may have the potential to improve efficacy. Type II L2 patients were the most difficult to cure.