To evaluate the application of laser lithotripsy under SpyGlass for difficult pancreatic duct stones. Data of patients who underwent laser lithotripsy under SpyGlass for difficult pancreatic duct stones from January 2018 to April 2020 in Shandong Provincial Third Hospital were collected. A total of 18 patients were included in the study and the number of endoscopic retrograde cholangiopancreatography (ERCP) performed on each patient was 1.5±0.7. The total operation success rate was 88.9% (16/18) and the number of SpyGlass lithotripsy was 1.3±0.4. The diameter of the stones was 13.17±3.69 mm and the number of stones was 1.70±0.74. Nine patients had stones located in the pancreatic head and 15 cases had stenosis of the proximal pancreatic duct. One case had post-ERCP pancreatitis. No bleeding, perforation or other complications occurred. The indwelling time of the pancreatic duct stent was 10.5±2.8 months, and the follow-up was 6-30 months. There was no recurrence of pancreatic duct stenosis or pancreatic duct stones. Laser lithotripsy under SpyGlass is safe and effective for difficult pancreatic duct stones.