Abstract BACKGROUND: It has been shown that ATP-sensitive potassium (KATP) channels play an important role in physiology of myocardial adaptation to ischemia. In cardiomyocytes, the pore-forming subunits of these channels are coded by KCNJ11 gene. It was reported that the common polymorphism E23K of this gene is associated with higher susceptibility to coronary heart disease (CHD) in Chinese patients, but no other reports are available from other ethnic groups. METHODS: Iranian patients with confirmed CHD, aged over 50 years were compared with healthy controls for allelic and genotypic frequencies of this polymorphism. Patients who did not suffer from diabetes mellitus were entered into this study if they showed coronary stenosis of > 50% in at least one artery in the angiography performed after a coronary event. The subjects and controls were matched for age, gender, blood glucose, body mass index and smoking. RESULTS: No association could be found between CHD and frequencies of G and A alleles, single genotype frequencies of AA, AG, GG, and combine genotypes frequencies of AG+AA versus GG, and AG+GG versus AA. CONCLUSION: This study did not find any association between coronary heart disease and E23K polymorphism in Iranian patients. But, this finding is not conclusive due to limitation of sample size. A subsequent study with a larger sample size is recommended. Keywords: Single Nucleotide Polymorphism, Kir6.2 channel, KATP Channels, Caucasian.