ObjectiveTo explore the application effects of hand-sewn layered anastomosis (HS) and circular stapled anastomosis (CS) in inflatable mediastinal mirror synchronous laparoscopic radical esophagectomy for esophageal cancer. MethodsPatients who underwent inflatable mediastinal mirror synchronous laparoscopic radical esophagectomy for esophageal cancer in Huaihe Hospital of Henan University from 2018 to 2019 were retrospectively included. Patients were divided into a HS group and a CS group according to the anastomosis methods, and propensity score matching was used to match patients at a ratio of 1:1. The baseline clinical characteristics, perioperative indicators, CD4+/CD8+ immune index comparison, pain, various lung function indicators, incidence of short-term and long-term postoperative complications, and quality of life were compared between the two groups. ResultsA total of 153 patients were included, including 108 males and 45 females, with an average age of (61.81±5.18) years. After propensity score matching, 70 patients were included in each group. Compared with the CS group, the operation time was longer in the HS group [(107.10±8.25) min vs. (97.65±6.85) min, P<0.001]; the CD4+/CD8+ level was lower in the HS group 1-3 days after surgery; the pain score was higher, and various lung function indicators (forced expiratory volume in the first second, forced vital capacity, and one-second rate) were lower in the HS group 1-7 days after surgery; within 6 months after surgery, the incidence of anastomosis-related complications (anastomotic stenosis, anastomotic fistula, and gastroesophageal reflux) was lower in the HS group; and the quality of life score was higher in the HS group from 14 days to 6 months after surgery (P<0.05). ConclusionHS can reduce the incidence of postoperative anastomotic fistula, anastomotic stenosis, and gastroesophageal reflux, and improve the short-term quality of life of patients, but it has a longer operation time, more intense short-term postoperative pain, and may affect the early recovery of lung function. HS and CS are complementary, and the appropriate surgical method should be chosen according to the individual situation of the patient to achieve the maximum clinical benefit.