EUS-guided gallbladder drainage has been increasingly applied for acute cholecystitis in high-risk surgical patients. In cases of EUS-guided gallbladder drainage with lumen-apposing metal stents (LAMSs), endoscopic retrieval of gallstones becomes feasible. However, retrieval of giant gallstones is still difficult because of the limited space in the saddle section of the LAMS. In this study, we aimed to evaluate the efficacy and safety of endoscopic laser lithotripsy and lithotomy through LAMSs for the removal of giant gallstones.