ObjectiveTo investigate the efficacy and safety of SpyGlass system combined with electrohydraulic lithotripsy during endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of difficult common bile duct stones. MethodsA total of 20 patients who used the SpyGlass system combined with electrohydraulic lithotripsy during ERCP for the treatment of difficult common bile duct stones in Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, from December 2019 to May 2020 were enrolled. Liver function, blood amylase, and blood lipase were measured after surgery; the patients were observed in terms of body temperature, abdominal pain, hematobilia, infection, and perforation; the presence or absence of residual common bile duct stones was reexamined after surgery. ResultsOf all 20 patients, 18 underwent successful lithotripsy on the first attempt without serious complications, and 2 underwent ERCP-guided basket extraction and biliary tract cleaning with balloon due to residual stones found in the reexamination after surgery and achieved complete removal of stones. No biliary tract perforation or massive hemorrhage was observed; there was mild pancreatitis after surgery, which was improved after pharmacotherapy; some patients had increased levels of blood amylase and lipase, without any clinical symptom; there was a significant improvement in liver function after surgery. Abdominal color Doppler ultrasound performed for all patients at 3 months after cholecystolithotomy showed no residual common bile duct stones. ConclusionSpyGlass system combined with electrohydraulic lithotripsy during ERCP has a high first-attempt success rate of complete removal of stones in the treatment of difficult common bile duct stones, without marked surgical complications.