Background: Current guidelines recommend screening for Esophageal Varices (EV) by Esophagogastroduodenoscopy (EGD) for all cirrhotic patients. The cost and invasive nature of endoscopic screening mean that there is an interest in developing noninvasive predictors for EV that would decrease the number of EGDs performed. The genetic factors that are involved in the development and maintenance of portosystemic collateral circulation have been rarely investigated. Variation at the genes that encode proteins involved in the systemic and splanchnic vasodilation, which include angiotensin-converting enzyme and endothelial/constitutive nitric oxide synthase, have been found to be involved in the EV risk among patients withcirrhosis. In cirrhosis, Vascular Endothelial Growth Factor (VEGF) receptor 2/VEGF and carbon monoxide (CO) activity are significantly increased and are closely correlated with porto-systemic collateral vasodilations. Haem-Oxygenase-1 (HO-1) is the main ratelimiting enzyme involved in CO production. Aim of Study:This study aimed at investigating the value of the genetic risk variants of HO-1, VEGF and VEGF Receptor-2 (VEGFR-2) in prediction of the presence of EV in patients with liver cirrhosis.Patients and Methods: Our study included 300 Egyptian patients with liver cirrhosis, aged 18 years or older, with no history of gastrointestinal bleeding, hepatic schistosomiasis, hepatocellular carcinoma, injection sclerotherapy or band ligation for EV, surgery for portal hypertension or portal or splenic vein thrombosis by ultrasonography. Patients underwent EGD to evaluate the presence and degree of EV, fibroscan for detection of liver stiffness and genetic investigation of HO-1, VEGF and VEGFR-2. Demographic, biochemical and endoscopic data were collected. Patients were divided into Group I (no varices), Group II A (small varices), Group IIB (large varices) and Group III (100 healthy control subjects).