Objective To investigate the efficacy and safety of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) for patients with acute cholecystitis who are unfit for cholecystectomy. Methods Patients who underwent EUS-GBD at Hangzhou First People’s Hospital from April 2015 to December 2016 were enrolled in this study. Clinical data were collected, and effectiveness and complications were analyzed. Results EUS-GBD was achieved in all 5 patients, and the mean procedure time of EUS-GBD was 26±3.1 min. Double pigtail plastic stents were successfully placed in 4 patients. A nasobiliary drainage tube was placed in 1 patient and the tube was endoscopically cut 5 days post-procedure acting as internal drainage. All patients recovered without complications and no procedure-related death occurred. During the follow-up period (46-692 d), no patient experienced recurrent cholecystitis and stent migration. Conclusion At an experienced endoscopic center, EUS-GBD is a safe, effective and minimally invasive method for patients with acute cholecystitis and high surgical risk.