This report describes the initial clinical implementation of a new laser lithotripter system capable of effective fragmentation of common bile duct stones with a high degree of safety provided by an integrated stone-tissue detection system. This system automatically terminates laser pulse transmission if tissue contact is sensed. Eighteen patients with giant or impacted common bile duct stones refractory to standard treatment techniques were treated via the endoscopic retrograde route using a rhodamine-6G dye laser with an integrated stone-tissue detection system. In the event of tissue contact, the stone-tissue detection system cuts off the laser pulse after 190 ns (after transmission of 5% to 8% of the total pulse energy). Nine patients were treated under cholangioscopic control, and nine patients were treated blindly under fluoroscopic control using only standard duodenoscopes with either a 6F standard endoscopic retrograde cholangiopancreatography catheter (4 patients), a 6.8F balloon catheter (3 patients), or a laser lithotriptor basket (2 patients). Laser-induced fragmentation was achieved in all 18 patients (100%). Sixteen of 18 patients (89%) became completely stone-free after completion of the treatment, including additional intracorporeal shock wave lithotripsy in five patients. The only major complications occurred in one fully anticoagulated patient with a prosthetic heart valve who developed significant hemobilia and transient cholangitis but recovered after conservative treatment. Laser lithotripsy using the rhodamine-6G dye laser plus stone-tissue detection system appears safe and effective and allows "blind" fragmentation of difficult common bile duct stones to be performed under radiologic control.