Gastric variceal bleeding is severe and is associated with high mortality. We compared the efficacy of cyanoacrylate injection and beta-blockers in primary prophylaxis of gastric variceal bleeding.Cirrhotics with large gastroesophageal varices type 2 with eradicated esophageal varices or large isolated gastric varix type 1, who had never bled from gastric varix, were randomised to cyanoacrylate injection (Group I, n=30), beta-blockers (Group II, n=29) or no treatment (Group III, n=30). Primary end-points were bleeding from gastric varix or death.The actuarial probability of bleeding from gastric varices over a median follow-up of 26 months was 13% in Group I, 28% in Group II (p=0.039), and 45% in Group III (p=0.003). The actuarial probability of survival was higher in the cyanoacrylate compared to the no-treatment group (90% vs. 72%, p=0.048). The median hepatic venous pressure gradient (HVPG) was increased in Group I (14-15 mm Hg, p=0.001) and III (14-16 mm Hg, p=0.001) but decreased in Group II (14 to 12 mm Hg, p=0.001) during follow-up. Size of gastric varix >20 mm, a MELD score ≥17, and presence of portal hypertensive gastropathy predicted 'high risk' of first bleeding from gastric varices.Primary prophylaxis is recommended in patients with large and high risk gastric varices to reduce the risk of first bleeding and mortality. Cyanoacrylate injection is more effective than beta-blocker therapy in preventing first gastric variceal bleeding.