Objective: To investigate clinical efficacy of percutaneous transhepatic endoscopy (PTES) combined with different lithotripsy methods for precision treatment of complicated hepatolithiasis and summarize relevant experiences. Methods: The clinical data of 49 patients with complicated hepatolithiasis undergoing PTES plus holmium laser lithotripsy or electrohydraulic lithotripsy were retrospectively analyzed. Results: The surgical successful rate was 93.9% (46/49). The average operative time was (107.5±8.9) min and blood loss was (43.6±10.4) mL. The incidence of residual stones was 8.7% (4/46) and complications occurred 18 times. The short- and long-term recurrence rate was 6.5% and 13.6%, respectively. Conclusion: PTES combined with different lithotripsy methods shows favorable efficacy in precision treatment of complicated hepatolithiasis. This method is recommended as the first choice of options for patients with no lobar atrophy, and the stones confined to one segment or one lobe of the liver as well as those without tolerance to an open surgery due to repeated biliary operation history.