Endothelial and microvascular dysfunction serve important roles in the formation and pathogenesis of cardiac syndrome X (CSX). Expression of receptor for advanced glycation end products (RAGE) is suggested to be increased in several conditions, including diabetes, inflammation and vascular diseases. In the present study, RAGE gene polymorphisms in patients with CSX and healthy controls were investigated. A total of 114 patients, diagnosed with CSX using coronary angiography results following complaints of angina and objective ischemia, and 103 healthy controls participated in the study. Whether there was a difference in genotype distributions of RAGE gene -374T/A, -429T/C and Glys82Ser polymorphisms between patients with CSX and healthy controls was investigated. Following DNA isolation from blood samples of the participants, the polymorphic regions were examined by quantitative polymerase chain reaction, and the genotyping results were statistically analyzed. When the genotypic distributions of -374T/A, -429T/C and Gly82Ser polymorphisms were investigated in patients with CSX and healthy controls, no statistically significant differences were identified between the two groups (P>0.05). Likewise, no statistically significant differences were observed in the allelic distributions of all 3 polymorphic regions (P>0.05). To the best of our knowledge, the present study also investigated the association between CSX and RAGE gene polymorphisms for the first time. No statistically significant differences in RAGE gene polymorphisms between the CSX and control groups were observed. We hypothesized that significant results may be obtained by increasing the numbers of patients and healthy controls in future studies.