Screening endoscopy is recommended for early detection of esophageal varices (EVs) in cirrhotic patients with portal hypertension. However, this approach is limited by its invasiveness and cost. The aim of the study was to determine if platelet count can predict the presence of EVs, especially large (grade III, IV) EVs in need of prophylactic therapy, in a cohort of Egyptian patients with liver cirrhosis. In all, 110 patients with cirrhosis were prospectively analyzed. The presence of medium or large EVs was correlated with patients' platelet count and FIB-4. Esophageal varices were present in 87 (79.09%) patients. Among those with thrombocytopenia (platelet level below 150,000), 25.97% (20 patients) and 27.27% (21 patients) had EV grade II and EV grade III or IV, respectively. Whereas in patients in whom the platelet count was above 150,000, only 21.21% (7 patients) and 9.09% (3 patients) of patients had grade II EV and EV grade III or IV, respectively. A platelet count cut-off value of 149,000 was found to have specificity of 82% and sensitivity 39% for detection of presence of varices. A FIB-4 cut-off value of 3.175 was found to have an 83.3% sensitivity and 39.5% specificity in detecting large (grade III, IV) EVs. Platelet count is a noninvasive parameter with high accuracy for prediction of EVs. Cirrhotic patients with normal platelet counts (above 150,000), especially in financially deprived developing countries, can avoid screening endoscopy as they are at a low risk for variceal bleeding, and presence of large EVs in these patients is much less common than in those with thrombocytopenia. A 3.175 cut-off value of FIB-4 could be useful as a noninvasive predictor of large varices requiring prophylactic banding in cirrhotic patients.