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Totally laparoscopic total gastrectomy has been developed with difficulty in intracorporeal esophagojejunostomy. Although mechanical stapling has been widely used for intracorporeal esophagojejunostomy, manual suture holds great promise with the emergence of high-resolution 3D vision and robotic surgery. After exploration of how to improve the safety and efficiency of intracorporeal suture for esophagojejunostomy, we recommended the technique of single-layer running "trapezoid-shaped" suture. The cost-effectiveness was analyzed by comparing with conventional mechanical stapling.The study retrospectively reviewed the patients undergoing laparoscopic gastrectomy for gastric cancer from January 2010 to December 2021. The patients were divided into two cohorts based on the methods of intracorporeal esophagojejunostomy: manual suture versus stapling suture. Propensity score matching was performed to match patients from the two cohorts at a ratio of 1:1. Then group comparison was made to determine whether manual suture was non-inferior to stapling suture in terms of operation time, anastomotic complications, postoperative hospital stay, and surgical cost.The study included 582 patients with laparoscopic total gastrectomy. The manual and stapling suture for esophagojejunostomy were performed in 50 and 532 patients, respectively. In manual suture cohort, the median time for the whole operation and digestive tract reconstruction were 300 min and 110 min. There was no anastomotic bleeding and stenosis but two cases of anastomotic leak which occurred at 3 days after surgery. The median length of postoperative hospital stay was 11 days. After propensity score matching, group comparison yielded two variables with statistical significance: time for digestive tract reconstruction and surgery cost. The manual suture cohort spent less money but more time for esophagojejunostomy. Intriguingly, the learning curve of manual suture revealed that the time for digestive tract reconstruction was declined with accumulated number of operations.Laparoscopic single-layer running "trapezoid-shaped" suture appears safe and cost-effective for intracorporeal esophagojejunostomy after total gastrectomy. Although the concern remains about prolonged operation time for beginners of performing the suture method, adequate practice is expected to shorten the operation time based on our learning curve analysis.