Introduction: Cardiovascular disease is the leading cause of mortality and morbidity all over the world. Among these cardiovascular deaths, half result from coronary artery disease (CAD). Increased prevalence of CAD is associated with increased levels of inflammatory markers. Phenotypic variations of these markers may depend on physiological stress or genetic variations. Materials and Methods: Single nucleotide polymorphism analysis of methylenetetrahydrofolate reductase (MTHFR), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) genes was done by PCR-DNA sequencing method. Results: Statistically significant elevation of inflammatory markers- homocysteine, hsCRP and fibrinogen were found in CAD group (p≤0.05). Multiple sequence alignment showed a single nucleotide mutation i.e., c.677 C>T (p. A222V) in exon-4 of MTHFR in 10% of CAD group and was associated with an increased risk of CAD (OR: 12.21). Mutations observed in exon-4 of IL-6 gene (in 26% of cases) was significantly associated with an increased risk of CAD (OR: 36.36). ICAM-1 (exon-6) mutation i.e., c.1405 A>G (p. K469E) was observed in 18% of patients and an increased risk of CAD (OR: 23.12). Conclusion: Polymorphisms observed in MTHFR, IL-6 and ICAM-1 genes in South- Indian ethnic population which are associated with elevated levels of inflammatory markers – homocysteine, hsCRP and fibrinogen appear to be predisposing factors for atherosclerosis.