Purpose: To evaluate the efficacy and safety of percutaneous transhepatic endoscopic holmium laser biliary lithotripsy (PTBL) to treat recurrent cholangitis due to intra/extrahepatic stones, in patients not candidate for traditional endoscopic treatment., Materials and Methods: We retrospectively evaluated 28 patients (M:F = 19:9, mean age = 65 years, SD = 14) undergoing 43 PTBL for stone-related recurrent cholangitis from January 1, 2012 to January 31, 2019 in a single academic center. Data collected included demographics, location and number of stones, clinical success after one (primary) or more than one (secondary) PTBL, procedure time, duration of hospital stay, number of retreatments and post-procedural complications. Clinical success was defined as the resolution of cholangitis at 30-day follow-up., Results: PTBL were successful for 23/28 (82%) patients, 16 (57%) with one and 7 (88%) with repeat procedures. The remaining 5 (18%) patients were finally treated with surgery (3, 11%) or further antibiotics (2, 7%). PTBL were performed to treat intrahepatic stones (22 treatments, 51%), extrahepatic (14, 33%), and both intra/extrahepatic (7, 16%). One to three stones were found in 12/43 (28%) PTBL, more than three in 31/43 (72%). Single PTBL was performed in 20/28 (71%) patients, two in 3/28 (11%), three in 3/28 (11%), and four in 2/28 (7%). Median procedure duration was 115 (29-210, 95% CI 101-129) minutes; median hospital stay was 5.5 (2-42) days. The only major complication was the breakage of a guidewire tip, surgically retrieved; minor complications included one aspiration pneumonia and three instances of intrahepatic hemorrhage, treated conservatively., Conclusions: PTBL was clinically successful in the 82% of patients not candidate for endoscopic treatment, with a low complication rate.