Esophageal squamous cell carcinoma (ESCC) is a prevalent and aggressive gastrointestinal tumor, particularly in East Asia. However, there is a lack of consensus on the long-term survival outcomes of intrathoracic anastomosis and cervical anastomosis following esophagectomy. This study aims to provide a comprehensive summary of the long-term survival outcomes of these two anastomosis techniques.We employed data drawn from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database from January 2010 to December 2017. Patients were stratified into two distinct groups according to the anatomical location of anastomosis following esophagectomy: those who underwent intrathoracic anastomosis (IA Group) and those who underwent cervical anastomosis (CA Group). To account for potential confounding factors and baseline imbalances between the two groups, propensity score matching (PSM) was employed.The CA Group exhibited longer OS compared to the IA Group, with a median OS of 49.10 months versus 35.87 months (HR,1.118; 95% CI: 1.118-1.412; P < 0.001) . Additionally, survival rates at 1-, 3-, and 5-years were higher in the CA Group (87%, 59%, and 48% respectively) compared to the IA Group (86%, 50%, and 39% respectively). The significance persisted even after propensity score matching (PSM) (HR: 1.164; 95% CI: 1.013-1.336; P < 0.001), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were applied. The survival difference between CA and IA was attributed to varying extents of lymph node dissection, particularly in the upper mediastinal zone (P < 0.001).In conclusion, our study suggests that there could be the potential survival advantage of CA over IA in patients undergoing esophagectomy for ESCC.Copyright © 2024. Published by Elsevier Inc.