Research is continuous for noninvasive tools for the prediction of portal hypertension than upper gastrointestinal endoscopy. Serum sCD163 correlates with hepatic venous pressure gradient, aiding in the prediction of portal hypertension. We aimed at investigating the role of sCD163 in the prediction of the presence and size of varices as well as a stratification tool for surveillance or prophylaxis by assessment of prognosis and risk of bleeding. Two hundred forty-three cirrhotic patients were divided into 3 groups: group I: no varices, group II: small-sized varices, and group III: medium-sized and large-sized varices. Serum sCD163 levels were assessed and correlated with abdominal ultrasound and laboratory investigations. Follow-up for 1 year was conducted to assess the risk of bleeding, and band ligation was performed for significant varices with follow-up of obliteration. sCD163 levels were significantly higher in patients with varices requiring prophylactic interventions (P = 0.03) and in large varices (P = 0.012), patients at risk of bleeding (P = 0.04), and the bleeder patients (P = 0.001). No relationship between the sCD163 levels and the rate of variceal obliteration was reported. sCD163 levels were positively correlated with the Child score (P = 0.05), the portal vein diameter (P = 0.02), and the splenic size (P = 0.04). Although sCD163 level cannot predict the development of varices, it serves as a good predictor for the detection of size of varices (large varices), the need of prophylactic interventions, and risk of variceal bleeding. sCD163 level is a helpful indicator with the progression of cirrhosis and portal hypertension.