Objective To evaluate the diagnostic and therapeutic effect of SpyGlass direct visualization system (SpyGlass) on cholangiopancreatic duct stenosis and large bile duct stones. Methods Patients with cholangiopancreatic duct stenosis or large bile duct stones of indeterminate reasons who underwent SpyGlass at Hangzhou First People's Hospital from September 2012 to August 2018 were recruited. Cholangiopancreatic duct stenosis were visually diagnosed using SpyGlass, and some patients underwent Spybite biopsy. Large bile duct stones were treated with SpyGlass-guided laser lithotripsy under direct visualization. The procedure success rate, clinical success rate, and adverse event incidence associated with SpyGlass were analyzed. Results SpyGlass was performed to diagnose and treat 114 patients with bile duct stricture, 11 patients with pancreatic duct stricture and 19 patients with large bile duct stones. The total procedure success rate was 98.6% (142/144). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SpyGlass visual diagnosis of bile duct stricture of indeterminate reasons were 97.1% (67/69), 95.3% (41/43), 96.4% (108/112), 97.1% (67/69), and 95.3% (41/43), respectively. The accuracy of SpyGlass visual diagnosis of pancreatic duct stricture of indeterminate reasons was 100.0% (11/11). Of the 19 patients with large bile duct stones, the lithotripsy success rate was 89.5% (17/19). The success rate of primary extraction was 73.7% (14/19), and that of secondary extraction was 100.0% (5/5). The total extraction success rate was 100.0% (19/19) Four patients (2.8%) had postoperative complications, including three cases of acute cholangitis and one case of mild acute pancreatitis. Conclusion SpyGlass is accurate and safe in the diagnosis of cholangiopancreatic duct stenosis. It is also effective and safe for treating large bile duct stones combined with laser lithotripsy.