Abstract： AIM: To determine if proton pump inhibitor use in cirrhotic patients with endoscopic findings of portal hypertension is associated with a lower frequency of gastrointestinal bleeding.METHODS: Patients with cirrhosis and endoscopic findings related to portal hypertension, receiving or not receiving proton pump inhibitor (PPI) therapy, were included retrospectively. We assigned patients to two groups: group 1 patients underwent PPI therapy and group 2 patients did not undergo PPI therapy.RESULTS: One hundred and five patients with a median age of 58 (26-87) years were included, 57 (54.3%) of which were women. Esophageal varices were found in 82 (78%) patients, portal hypertensive gastropathy in 72 (68.6%) patients, and gastric varices in 15 (14.3%) patients. PPI therapy was used in 45.5% of patients (n=48). Seventeen (16.1%) patients presented with upper gastrointestinal bleeding; in 14/17 (82.3%) patients,bleeding was secondary to esophageal varices,and in 3/17 patients bleeding was attributed to portal hypertensive gastropathy. Bleeding related to portal hypertension according to PPI therapy occurred in 18.7% (n=9) of group 1 and in 14% (n=8) of group 2 (odds ratio: 0.83, 95% confidence interval: 0.5-1.3, P=0.51).CONCLUSION: Portal hypertension bleeding is not associated with PPI use. These findings do not support the prescription of PPIs in patients with chronic liver disease with no currently accepted indication.