Objective To study the effect of primary-suture thriple-endoscope therapy on stone clearance rate and safety in patients with cholecystolithiasis and common bile duct stones. Methods This study collected 136 patients who received treatment of cholecystolithiasis and common bile duct stones in our hospital from January 2015 to June 2016. The patients were divided into an observation group and a control group with 68 cases in each group according to the digital random table method. The observation group was given primary-suture thriple-endoscope therapy, while the control group was given open surgery. The surgical indicators, success rate of surgery, stone clearance rate, surgical complications, and the levels of inflammatory cytokines before operation and 5 days after surgery including interleukin 6 (IL-6), interleukin 10 (IL-10) and C reactive protein (CRP) were compared between the two groups. Results The operation time, incision length, gastrointestinal recovery time and time of hospital stay were significantly shorter, the intraoperative blood loss was less in the observation group than in the control group (P < 0.05). The success rate of surgery and stone clearance rate were not significantly different between the two groups (P > 0.05). The total incidence of complications in the observation group was 2.94%, which was significantly lower than 11.76% in the control group (P < 0.05). The differences of IL-6, IL-10 and CRP levels before operation and 5 days after operation in the observation group were smaller than those in the control group (P < 0.05). Conclusions The primary-suture thriple-endoscope therapy has good effect in the treatment of cholecystolithiasis and common bile duct stones with high stone clearance rate and safety, and is worth to be popularized.