Objective: Coronary artery disease (CAD) is a Multifactorial and Heterogenic disease. During this disease atherosclerosis plaques have been formed in internal wall of coronary artery. This event result to limitation of blood reaching to myocardium. Reduction of blood flow may lead to appearance of some problems such as ischemia, sudden thrombosis veins and myocardial infarction (MI). This disease is the most prevalent heart disease as more than 65000 people in United States died by cardiovascular disease like MI in the 2008 year. Several environmental and genetic factors involved in the appearance of this disease that the most important of them include Hypertension, high LDL-C, age, mellitus diabetes, family history of early-onset heart disease and smoking. Many genes and loci, such as the 9p21 locus is believed to be involved in the etiology of the disease. According to Genome Wide Association Studies (GWAS), five polymorphisms in the 9p21 locus seem to be associated with the CAD. One of these polymorphisms is rs10757274 SNP that has shown remarkable association in several studies. Materials and Methods: We collected blood samples from 170 CAD patients and 100 healthy persons as control from the Golestan and the Aria Hospitals in Ahvaz. In this study association of rs10757274 (A/G) polymorphism with CAD was evaluated by Tetra ARMS PCR technique. Results: The frequencies of AA, AG and GG genotypes in patients were respectively 8.2%, 58.3% and 33.5% and in control cases were 35%, 63% and 2% respectively. GG Genotype in rs10757274 polymorphism was found in CAD patients more than control cases (Odd Ratio (OR): 0.014, 95% CI: 0.003 -0.065, p value: 0.0001). Conclusion: The rs10757274 Polymorphism on chromosome 9p21 is significantly associated with CAD. This variant may help the identification of patients with increased risk for coronary artery disease.