Background: Portal hypertension (PHT) is a frequent clinical syndrome arising as a sequela of mesenchymal dysfunction in a cirrhotic liver. Esophageal varices (EV) are portosystemic collaterals in the submucosa of the lower esophagus. Heme oxygenase -1 (HO-1) was suggested as having vascular effects. So, in our study, we aimed to evaluate the role of HO-1 promotor polymorphism (rs2071746) on esophageal varices among patients with cirrhosis. Objectives: The present study was designed to evaluate the role of HO-1 SNP 413A>T promoter (rs2071746) polymorphism in the development of esophageal varices among cirrhotic patients. Patients and methods: A total of 105 subjects, including 35 cirrhotic patients with esophageal varices, 35 cirrhotic patients without esophageal varices, and 35 healthy controls were selected. HO-1 rs2071746 polymorphism was studied using Real-Time polymerase chain reaction (Real-Time PCR). Results: we found that AA, AT, AA+AT genotypes were significantly associated with an elevated risk of EV development (OR =6.82, 95% CI =1.24- 37.54), (OR= 6.43, 95% CI =1.21- 34.19), (OR= 6.60, 95% CI=1.33- 32.84) respectively. And, the A allele was correlated with an increased risk of EV (OR= 2.06, 95% CI=1.40- 4.10). Patients with the AA genotype were significantly associated with lower platelet levels (P= 0.026), lower platelets count/ spleen diameter ratio (p-value= 0.014). Also, they had large varices (p-value= 0.025). Conclusion: Our results suggest rs2071746 polymorphism could be used as a potential predictor and early diagnostic marker of EV development.