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Objective This study aimed to compare the effects of continuous hand-sewn esophagojejunostomy with barbed suture and mechanical anastomosis in total laparoscopic gastrectomy for esophagogastric junction cancer. Materials and methods The clinical data of 60 patients who underwent total laparoscopic total gastrectomy from January 2020 to October 2021 were collected retrospectively. Baseline data and short-term surgical results of patients in the hand-sewn anastomosis (n = 30) and mechanical anastomosis (n = 30) groups were analyzed. Results No significant differences were detected in the baseline data between groups. Meanwhile, the hand-sewn group had a shorter anastomosis time (21.2 ± 4.9 min vs. 27.9 ± 6.9 min, p < 0.001) and a decreased operation cost (CNY 70608.3 ± 8106.7 vs. CNY 76485.6 ± 3149.9, p = 0.001). The tumor margin distance in the hand-sewn group was longer than in the mechanical group (2.7 ± 0.4 cm vs. 2.2 ± 0.75 cm, p = 0.002). In esophagojejunostomy anastomosis, the distance between the jejunal opening and jejunal stump in the hand-sewn group was significantly shorter than that in the mechanical group (2.2 ± 0.54 cm vs. 5.7 ± 0.6 cm, p < 0.001). No significant difference was detected in the incidence of postoperative anastomotic complications. Conclusion The continuous hand-sewn anastomosis with barbed suture in total laparoscopic gastrectomy for esophagogastric junction cancer is practical, safe, and cost-effective. It is also an effective supplementary technique for mechanical anastomosis.