Background and study aims: Percutaneous transhepatic cholangioscopy (PTC) is being increasingly used for patients with biliary tract diseases. The aim of this study was to assess the safety of this procedure, and we systematically analyzed PTC-related complications and the risk factors for those complications. Patients and methods: A total of 364 patients who underwent PTC were included in the study. The initial diagnoses, the indications for PTC, the complications that occurred during the procedures, and the risk factors for these complications were retrospectively analyzed. Results: The overall incidence of complications was 12.9 % for percutaneous transhepatic biliary drainage (PTBD), 12.8 % for tract dilation, and 6.9 % for tract maturation. Complications developed in 58/848 PTC sessions (6.9 %). Cholangitis and bacteremia were associated with PTBD and tract dilation, catheter migration and blockage with tract maturation, and bile duct injury with PTC. Mild complications occurred in 80 patients (22.2 %) during the preparation stages and in 43 sessions (5.1 %) during the PTC itself. Severe complications, including severe hemobilia, hemoperitoneum, rupture of the sinus tract, and ductal injury developed in 17 patients (4.7 %) during the preparation period, and in 15 patients (4.1 %) during PTC. The overall incidence of severe complications along the entire course was 8.2 % (30/364 patients). No patient died or required surgery. Intraductal manipulations, such as electrohydraulic lithotripsy or balloon dilation, and the first session of PTC were risk factors for procedure-related complications. Conclusions: PTC is a relatively safe and well-tolerated method for treating certain biliary tract diseases. Meticulous patient selection and a cooperative team approach are required in order to minimize the incidence of complications and to provide effective management.