Objective To investigate the feasibility and safety of endoscopic trans-gastric gallbladder-preserving cholecystolithotomy (ETGC) for gallstones. Methods The clinical data of 84 cholecystolithiasis patients, who received ETGC at Endoscopic Center of Zhongshan Hospital from March 2017 to May 2019 were analyzed retrospectively. The operation completion rate, operation time, complications and recurrence of calculus were summarized. Results In the 84 cases of cholecystolithiasis, there were 19 cases (22.6%) of single stone, 53 cases (63.1%) of multiple stones, and 12 cases (14.3%) of gallstones with gallbladder polyps. A total of 82 patients (97.6%) successfully completed ETGC with median operation time of 88 min. Ten patients (12.2%) suffered from abdominal pain after operation, of which 6 patients relieved after conservative treatments. The other 4 cases, including 2 cases of hemoperitoneum, 1 case of biliary fistula, and 1 case of choledocholithiasis with obstructive jaundice, were recovered after corresponding interventions. As of June 14, 2019, 5 cases were lost to follow-up (follow-up rate was 93.9%, 77/82). Residual stones were found in 2 cases (2.6%, 2/77). Stone recurrence was discovered in 4 cases (5.2%, 4/7), and 2 cases (2.6%, 2/77) had cholesterol crystallization in gallbladder. Conclusion ETGC is minimally invasive, feasible and safe in treatment of cholecystolithiasis, and can retain the function of gallbladder. However, how to completely remove the stones and avoid residue by ETGC still needs further exploration, and its long-term efficacy still needs further observation.