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Fourteen patients who failed at least 1 endoscopic retrograde cholangiopancreatograpy attempt underwent Holmium laser biliary lithotripsy between 2003 and 2007. Ten had prior biliary surgeries, 7 harbored multiple stones, and 6 had common bile duct strictures. Mean age at surgery was 63.6 years (50 to 80 y), biggest stone burden 30 mm, mean operative time 58.4 minutes (24 to 105), and stone free rate 85.7%. One patient had postoperative bleeding from the choledochostomy tube that eventually resolved spontaneously and 3 patients had postoperative cholangitis managed conservatively. Neither conversions to open surgery nor mortality was recorded. Two patients were diagnosed with cholangiocarcinoma missed by previous endoscopic retrograde cholangiopancreatograpy. After a mean follow-up of 18.9 months (2 to 43) no de novo strictures were recorded. Percutaneous choledochoscopy with holmium laser lithotripsy is a safe and effective minimally invasive technique to treat complex biliary stone disease and may preclude high-risk open biliary tract surgery.