OBJECTIVE Advances in endoscopic techniques have transformed the management of urolithiasis. We sought to evaluate the role of such urological interventions for the treatment of complex biliary calculi. METHODS We conducted a retrospective review of all patients (n=9) undergoing percutaneous holmium laser lithotripsy for complicated biliary calculi over a 4-year period (12/2003 to 12/2007). All previously failed standard techniques include ERCP with sphincterotomy (n=6), PTHC (n=7), or both of these. Access to the biliary system was obtained via an existing percutaneous transhepatic catheter or T-tube tracts. Endoscopic holmium laser lithotripsy was performed via a flexible cystoscope or ureteroscope. Stone clearance was confirmed intra- and post-operatively. A percutaneous transhepatic drain was left indwelling for follow-up imaging. RESULTS Mean patient age was 65.6 years (range, 38 to 92). Total stone burden ranged from 1.7 cm to 5 cm. All 9 patients had stones located in the CBD, with 2 patients also having additional stones within the hepatic ducts. All 9 patients (100%) were visually stone-free after one endoscopic procedure. No major perioperative complications occurred. Mean length of stay was 2.4 days. At a mean radiological follow-up of 5.4 months (range, 0.5 to 21), no stone recurrence was noted. CONCLUSIONS Percutaneous endoscopic holmium laser lithotripsy is a minimally invasive alternative to open salvage surgery for complex biliary calculi refractory to standard approaches. This treatment is both safe and efficacious. Success depends on a multidisciplinary approach.