Esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), is a major health concern worldwide, particularly in China. Surgical resection is still considered the primary curative treatment for this disease. However, the effect of different surgical methods-traditional hand-sewn anastomosis and modern mechanical anastomosis-remains controversial. A retrospective study was thus performed to elucidate how these two techniques affected the clinical prognosis of patients. Data were retrospectively collected from the comprehensive Esophageal Cancer Case Management Database of Sichuan Cancer Hospital and Institute (Chengdu, China), covering the period from 2010 to 2017. The cohort consisted of patients who underwent esophagectomy for ESCC, divided into two groups based on the suturing technique used: Manual suturing (MS) and mechanical suturing (MeS). A total of four causal inference methods for retrospective studies, namely inverse probability of treatment weighting, standardized mortality ratio weighting, overlap weighting and propensity score matching analysis, were used to minimize potential selection bias. The primary outcome evaluated was overall survival (OS), allowing for a direct comparison of the long-term efficacy of the two suturing methods. In a retrospective analysis of 2,510 patients undergoing esophagectomy, significant differences in OS were observed between the MeS group and the MS group (hazard ratio: 0.84; 95% confidence interval: 0.75-0.95; P=0.004). However, after matching or weighting based on causal inference analyses, no significant differences in survival outcomes between groups were obtained. The equivalence in outcomes suggests that either suturing method may be equally viable in clinical practice, offering flexibility in surgical decision-making without compromising OS.