ABSTRACT Background: Bleeding of esophageal varices (OV) is also bearing elevated mortality in patients with liver cirrhosis (LC). The best standard diagnostic investigation for OV is upper gastrointestinal (GI) endoscopy. Patients and endoscopic units alike are burdened by the endoscopic screening of all patients with liver cirrhosis. The use of non-invasive OV detection reduces the need for endoscopic screening. Objective: The aim of the current work was to test serum soluble CD 163(sCD163) as a predictor of the presence, and grade of OV and as non-invasive indicator of having severe variceal bleeding. Patients and Methods: This cross-sectional study included a total of 70 cirrhotic patients, attending at the Hepatology and Gastroenterology Unit, Department of Internal Medicine, Benha University Hospital, Egypt. To detect OV, all patients underwent upper GI endoscopy, and serum sCD163 levels were assessed using an ELISA technique. Results: Patients with OV had a higher mean value of sCD163 levels (8.71±8.42 ng/ml) than patients without OV (2.89±1.02 ng/ml), however this was not statistically significant (P=0.13). sCD163 level was significantly higher in large OV group (10.75±9.26 ng/ml) than small OV group (3.75±0.92 ng/ml), (P=0.001). The rate of significant variceal bleeding is closely linked to serum higher sCD163 levels more than (4.63 ng/ml). Conclusion: It could be concluded that serum sCD163 could be a non-invasive indicator of the presence of OV in cirrhotic patients. It may also be used for the prediction of the size of OV and the probability of severe variceal bleeding.