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Background Tumor necrosis factor-alpha (TNF-α) are considered as a pro inflammatory and interleukin-10 (IL-10) anti inflammatory have been shown to predict the risk of incident of coronary artery disease (CAD). The polymorphism at promoter of TNF-α and IL-10 has been shown to increase transcriptional activity of the gene and play a important role in patho physiology of CAD. Aim of present study is to examine the impact of the TNF-α and IL-10 variant allele on various markers of the CAD and to study its relation with circulating TNF-α and IL-10 levels. Methods The −308 G/A & −238 G/A of TNF-α and −1082 G/A & −819 C/T of IL-10 gene polymorphism has been studied in 301 diagnosed CAD subjects (Age 51.50 ± 9.28; BMI 25.30 ± 3.58) and 305 healthy controls (Age 51.57 ± 9.50; BMI 24.06 ± 7.26). These polymorphism of TNF-α and IL-10 were detected by real time PCR by using Taqman SNP genotyping assay. Furthermore serum TNF-alpha and IL-10 levels were also measured by ELISA. Results Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls ( p  > 0.05). On allele contrast, significant association with susceptibility to CAD was detected with polymorphisms in TNF-α -308 G/A, that variant genotype GA + AA (dominant model) (p = 0.030: OR = 1.61: 95% CI = 1.06–2.44) and variant allele (A) (p = 0.006: OR = 1.71: 95% CI = 1.17–2.51) of TNF-α 308 G/A gene was significant highly observed in the cases as compared to control group. Furthermore, variant genotype CT + TT (dominant model) (p = 0.004: OR = 1.62: 95% CI = 1.17–2.24) and variant allele (T) (p < 0.001: OR = 1.49: 95% CI = 1.17–1.89) of IL-10 −819 C/T gene was significant highly observed in the cases as compared to control group. Conclusion Our results suggest that the TNF-α G-308A polymorphism independently associated with DBP, cholesterol, triglyceride, LDL, TNF-α and IL-10 levels which may be leads to the development of coronary artery disease of North Indians. [ABSTRACT FROM AUTHOR]