Objective To analyze the effect comparison of different primary suture methods in the combined treatment of common bile duct stones with double endoscopy. Methods:120 patients with common bile duct stones admitted to our hospital from March 2022 to January 2025 were selected as the research subjects. The patients were randomly divided into the control group and the observation group, with 60 cases in each group. Both groups underwent combined double-mirror surgery. On this basis, different suture methods were adopted in the two groups. The control group was subjected to intermittent suture with myrtle buckwheat thread, while the observation group was subjected to continuous suture with barb thread. The perioperative indicators (operation time, blood loss, indwelling drainage tube, pain degree, hospital stay), stress indicators [adrenocorticotropic hormone (ACTH), cortisol (Cor), norepinephrine (NE)], inflammatory factors [interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT)], complications, residual stone rate, recurrence rate and quality of life [Comprehensive Quality of Life Assessment Questionnaire (GQOLI74)] of the two groups were analyzed and compared.? Results: The operation time, indwelling drainage tube and hospital stay of the observation group were significantly shorter than those of the control group, the amount of bleeding was significantly less than that of the control group, and the VAS score was significantly lower than that of the control group (P < 0.05). At 12 hours after the operation, the levels of ACTH, Cor and NE in both groups were significantly increased compared with those before the operation, but the levels of ACTH, Cor and NE in the observation group were significantly lower than those in the control group (P < 0.05). At 12 hours after the operation, the levels of IL-6, CRP and PCT in both groups were significantly increased compared with those before the operation, but the levels of IL-6, CRP and PCT in the observation group were significantly lower than those in the control group (P < 0.05). There was no significant difference in the incidence of complications between the two groups (P > 0.05). There was no significant difference in the residual rate and recurrence rate of stones between the two groups (P > 0.05). The scores of various quality of life items such as physiological function, physical pain, mental health and general health in the observation group were significantly higher than those in the control group (P < 0.05). Conclusion: The application of continuous suture with barb thread during the combined treatment of common bile duct stones by double endoscopy can optimize perioperative indicators, alleviate pain and stress responses, relieve inflammation, and improve the quality of life.