Objective To evaluate the efficacy and safety of endoscopic ultrasound (EUS)-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt. Methods Data of 24 patients with gastric fundal varices with large spontaneous shunt (the smallest diameter was 5-15 mm) treated by EUS-guided coil embolization combined with endoscopic cyanoacrylate injection in Renmin Hospital of Wuhan University from December 2016 to December 2020 were retrospectively analyzed. The short-term efficacy (the rates of technical success, five-day rebleeding and six-week mortality) and long-term efficacy (the rates of one-year rebleeding, one-year mortality and three-year mortality) and safety (ectopic embolism) were evaluated. Results The technical success rate was 91.7% (22/24), and the five-day rebleeding rate was 0 (0/22). Computed tomography angiography of portal vein reexamined 2 days after the treatment showed embolism of splenic vein in 1 patient (4.5%). The median follow-up time was 14.9 months (ranging 1.0-48.6 months) and 2 patients were lost during follow-up. The six-week mortality was 0 (0/20), and the one-year rebleeding rate was 35.0% (7/20). Among 12 patients who underwent endoscopy in the follow-up, 5 had aggravation of esophageal varices, and 5 had aggravation of portal hypertension gastropathy. The one-year and three-year mortalities were 5.0% (1/20) and 20.0% (4/20), respectively, neither of which was related to such events as bleeding or ectopic embolism. Conclusion EUS-guided coil embolization combined with endoscopic cyanoacrylate injection for gastric fundal varices with large spontaneous shunt is effective and safe in short term, with a low rate of ectopic embolism. Long-term efficacy and safety need to be further confirmed.