Background: Progression of coronary artery disease (CAD) depends on multiple genetic and environmental factors. Polymorphic variants of genes encoding proteins involved in endothelium dysfunction or proinflammatory state may genetically differentiate the human population and determine a susceptibility to the disease. Aim: To find the relationship between single polymorphisms of MTHFR, IL-6 and ICAM1 genes, double or triple combinations among their polymorphic variants and CAD in a patient population from the Upper Silesia region. Methods: The study population consisted of 177 patients with angiographically documented CAD and 202 blood donors with no signs of CAD. All examined individuals were white Polish Caucasians aged 18-55 years. The analysis of genetic polymorphisms was performed using the PCR-RFLP method. Results: We observed a weak association between single gene polymorphism and the disease only in the case of the MTHFR T allele. We also found that the frequency of some double or triple combinations among analysed genes, especially for MTHFR+ICAM1 and MTHFR+ICAM1+IL-6 patterns, differentiated the entire patient group from controls (p=0.047 OR=1.75 and p=0.016 OR=1.75, respectively). These two combinations were also significantly more frequent in patients who were age-matched with controls, especially in the female subgroups (for MTHFR+ICAM1 p=0.007, OR=10.32 and for MTHFR+ ICAM1+IL-6, p=0.005, OR=17.95 in females). Conclusion: The present study showed that simultaneous carrier-state of MTHFR, IL-6 and ICAM1 genes increased the risk of CAD.