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Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been introduced as an alternative to percutaneous transhepatic gallbladder drainage for the treatment of acute cholecystitis in non-surgical candidates. A systematic review of the English language literature through PubMed search until June 2014 was conducted. One hundred and fifty-five patients with acute cholecystitis treated with EUS-GBD in eight studies and 12 case reports, and two patients with EUS-GBD for other causes were identified. Overall, technical success was obtained in 153 patients (97.45%) and clinical success in 150 (99.34%) patients with acute cholecystitis. Adverse events developed in less than 8% of patients, all of them managed conservatively. EUS-GBD has been performed with plastic stents, nasobiliary drainage tubes, standard or modified tubular self-expandable metal stents (SEMS) and lumen-apposing metal stents (LAMS) by different authors with apparently similar outcomes. No comparison studies between stent types for EUS-GBD have been reported. EUS-GBD is a promising novel alternative intervention for the treatment of acute cholecystitis in high surgical risk patients. Feasibility, safety and efficacy in published studies from expert centers are very high compared to currently available alternatives. Further studies are needed to establish the safety and long-term outcomes of this procedure in other practice settings before EUS-GBD can be widely disseminated.