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Objective: We investigated the impact of direct peroral cholangioscopy (POC)-based holmium laser lithotripsy using an ultrathin endoscope with direct irrigation via a 2-mm-diameter working channel to remove difficult common bile duct (CBD) stones without a separate biliary catheter. Background data: Few clinical studies have reported the successful removal of difficult CBD stones by direct POC-based laser lithotripsy using an ultrathin upper endoscope. Previous studies used a separate biliary catheter to ensure continuous irrigation. Methods: Ten patients (6 males; mean age 63.3 years) with difficult CBD stones who were not amenable to conventional endoscopic procedures were examined. Direct POC using an ultrathin upper endoscope was performed in all patients. Holmium laser lithotripsy with direct saline irrigation via the operating channel of an ultrathin endoscope was performed until stone fragments were captured in a basket. Results: The overall success rate of bile duct clearance was 90% (9 of 10 patients) and the mean number of treatment sessions was 1.2 (range, 1–2). Mechanical lithotripsy was performed to complete stone removal in one patient (10%) who had a distal CBD stricture. One patient experienced mild cholangitis following laser lithotripsy. Conclusions: Holmium laser lithotripsy under direct POC using an ultrathin upper endoscope may be an effective and safe technique for removal of difficult CBD stones. Direct irrigation via the 2-mm-diameter working channel of the ultrathin endoscope provides sufficient fluid medium and affords good endoscopic viewing to assure stone fragmentation without any need for a separate biliary catheter.