Objective To evaluate the efficacy and safety of SpyGlass direct visualization system (DS) in treatment of patients with difficult choledocholithiasis after removing failure through endoscopic retrograde cholangiopancreatography (ERCP) and surgical approach. Methods The clinical data of 8 patients with choledocholithiasis who had undergone lithotripsy with SpyGlass DS combined with ERCP in department of surgery Ruijin Hospital, from January 2020 to December 2021 were analyzed retrospectively. The diagnosis and treatment and adverse events incidence were evaluated. All cases were with difficult choledocholithiasis. Seven cases had removal stone failure of ERCP including 4 cases with 1 time, 1 case with 5 times, and the other 2 cases with 6 times. One case had history of surgical treatment failure. Results A total of 8 cases received 10 times of Spyglass DS procedures with all cases successful visualization of bile duct stones and complete stone removal. Four cases (50%) underwent successful stone removal at the first procedure. The other 4 cases (50%) were successful stone removal after treatment again from 1 week to 4 months post procedures. One case was diagnosed both common bile duct stone and bile duct tumor and treated by surgery after endoscopy. There were 2 cases (20%) with slight epigastric pain, 3 cases (30%) with fever, 1 case (10%) with hyperamylasemia, 4 cases (40%) with abnormal liver function and 1 case (10%) with acute cholangitis. All cases with symptom were mild and improved after treatment. No procedure-related pancreatitis, gastrointestinal perforation or massive hemorrhage was found. Conclusions SpyGlass DS with ERCP and lithotripsy would be effective and safe in diagnosis and treatment of the patients with difficult choledocholithiasis who had previous treatment failure by conventional methods.