Background: Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide. There are many risk factors for CHD but recently the role of oxidative stress in progression of atherosclerosis has been more recognized. Paraoxonase 1 (PON1) protects against oxidation of LDL and many polymorphisms in both of exons and promoter regions of (PON1) gene have been investigated for their association with CHD. The aim of the present study was to investigate the relation between CHD suceptibility and PON1 Q192R (A/G) gene polymorphism in a cohort of Egyptian individuals. Methods: The study included 100 subjects, 50 patients who admitted to cardiovascular department with established diagnosis of obstructive coronary artery disease by coronary angiography and 50 healthy participants. Genotyping of PON1 Q192R (A/G) was done, and then serum concentration of PON1 was assessed by ELISA after that by spectrophotometer. Results: Serum PON1 enzyme was lower in patients with CHD than in control group with a statistically significant difference p < 0.001. A statistically significant association was observed with AG and GG genotypes of PON1 gene with CHD with P= 0.003, OR=5.02(95% CI =1.66-15.26) and P= 0.038, OR= 9.4 (95% CI =1.07-82.5); respectively. The G allele of PON1 was higher in CHD patients than controls suggesting that this allele may demonstrate a susceptibility effect to CHD in our cohort with P<0.001, OR= 5.16 (95% CI = 2.1-12.5) Conclusion: The Q192R polymorphism in the PON1 gene may be a susceptibility gene associated with increased risk of CHD among Egyptians.