Objective: Coronary artery disease (CAD) represents the most important cause of sudden cardiac death. More than 80% of sudden cardiac deaths are caused by atherosclerotic CAD. Genetic studies of CAD and MI are lagging behind other cardiovascular disorders. The major reason for the limited success in the field of CAD/MI genetics is that CAD or MI is a complex disease, which is believed to be caused by many genetic factors, environmental factors, and interactions among these factors. Recently, a mutation in the human MEF2A gene was reported to be responsible for an autosomal dominant form of coronary artery disease, so the purpose of the present study was to assess the significance of MEF2A mutations in Iranian subjects with coronary artery disease (CAD). Materials and Methods: CAD patients were recruited from the patient population of the Tehran Heart center. CAD was defined as documented myocardial infarction and/or angiographic vidence of at least two coronary artery with more than 50% stenosis. The majority of subjects had a history of severe CAD and had undergone coronary artery bypass grafting. Primer were designed to cover all the coding regean of exon 11 MEF2A gene. The exon 11 MEF2A gene was sequenced in CAD patients from 10 CAD families (and their unaffected members). Results: The study was performed in two stages: first to determine the MEF2A gene variants prevalent in the Iranian families, followed by investigating their impact on CAD manifestation. No mutation was identified in any of these extended families. We found new variations in Iranian families those not related to disease. Conclusion: We determined the MEF2A gene variants and their association with CAD in a cohort of patients established disease in the Iranian population. The distribution of the allele frequencies of MEF2A exon 11 CAG repeat (CAG)n polymorphism was similar in both patients and controls; Further, no significant association was noted between MEF2A exon 11 (CAG)n polymorphism and the risk of myocardial infarction.