Purpose of the study: To report our experience in treating complicated biliary calculi by percutaneous transhepatic endoscopic biliary holmium laser lithotripsy (PTBL). Patients and Methods: Ten symptomatic patients with intrahepatic or common bile duct calculi underwent PTBL. Six of these patients had previously undergone unsuccessful endoscopic treatment; four patients were declared not suitable for endoscopic procedure. PTBL was performed with a flexible choledochoscopy inserted by way of the percutaneous access sheath. A holmium laser was used to fragment the biliary stones. Sphincteroplasty was performed when considered necessary and an occlusion balloon for the clearance of common bile duct (CBD) calculi was used when continuous warm saline irrigation at high pressure was not sufficient. Clinical follow up was performed by the referring physician. Technical success, clinical success and complications were evaluated. Main findings: Technical success rate was 100%. The overall clinical success rate was 100%. No patients underwent additional procedures for retained stones or developed de novo strictures or other complications related to the procedure. Hospital stay was no more than 4 days after the procedure. Duration of follow-up was 6-25 months (mean 12.6). One patient died from unrelated causes. During this period, no recurrence and/or complications related to procedure were observed.No major complications were registered. Minor complications like temporary abdominal pain were considered not significant by the patients. Conclusions: Complicated or large biliary calculi can be treated successfully using PTBL. In selected patients, this approach should become the first choice of treatment after other treatments are rejected.