OBJECTIVES: To investigate the clinical characteristics, risk factors, and predictors of esophagogastric variceal bleeding in patients with hepatitis C virus (HCV)-induced liver cirrhosis. METHODS: This comparative observational study was carried out on 100 patients suffering from post hepatitis cirrhosis and portal hypertension who were admitted to the Internal Medicine Department, Al-Azhar University Hospital, Damietta Egypt. Patients were classified into two groups: 50 of them presented with esophagogastric varices with acute variceal bleeding, and 50 patients presented without bleeding. Data were collected, coded, revised, and entered into the Stata software version 16. RESULTS: The mean age of patients with bleeding was slightly higher than those without bleeding (55.58 ± 5.89 vs. 52.54 ± 9.01 years), p = 0.049. Mild ascites, positive H.Pylori, and Child-Pugh score B and C were an independent predictors of esophagogastric variceal bleeding (OR = 0.036, 95% CI: 0.0004-0.36; p = 0.005), (OR = 7.36, 95% CI: 1.44-37.59; p = 0.016), (OR = 19.0, 95% CI: 2.02-186.3; p = 0.010), and (OR = 40.51, 95% CI: 2.18-751.31; p = 0.013). The sensitivity of this model was 93.88%, specificity was 53.85%, PPV was 88.46%, NPV was 70.0%, correctly classified patients were 85.48%, and AUC was 90.27%. In the second model, pepsinogen level higher than 43.5 μg/l, AST (>54.5), Bilirubin (>1.45), and Hemoglobin (>11.5) were a significant independent predictors of esophagogastric variceal bleeding (OR = 1.18, 95% CI: 1.09-1.27; p<0.001), (OR = 1.14, 95% CI: 1.03-1.27; p = 0.007), (OR = 5.55, 95% CI: 1.21-25.43; p = 0.027), and (OR = 0.05, 95% CI: 0.008-0.32; p = 0.002), respectively. The sensitivity of this model was 92%, specificity was 98%, PPV was 97.87%, NPV was 92.45%, correctly classified patients were 95%, and AUC was 98.68%. CONCLUSION: The independent predictors of esophagogastric variceal bleeding were ascites, positive H. pylori, Child-Pugh score B and C, pepsinogen level higher than 43.5 μg/l, AST (>54.5), bilirubin (>1.45), and hemoglobin (>11.5). Laboratory investigations are more reliable in predicting variceal bleeding and excluding non-variceal bleeding; however, clinical symptoms should not be neglected, especially H. pylori infection, ascites, and Child-Pugh score.