Background: Cardiovascular diseases (CVDs) are diseases that affect the heart or vessels. Coronary artery disease (CAD) and peripheral (PAD) are types of CVD. PON1 is a HDL-associated lipolactonase is considered to be atheroprotective by preventing LDL and cell membranes oxidation. A common polymorphism due to an amino acid substitution (Glutamine  Arginine) at codon 192 is considered to be a major determinant of variation in serum PON1 activity. Recent studies have suggested that the PON1192 polymorphism is an independent risk factor for CVD Objectives: The effect of the PON1 activity and PON1 Q192R (rs662) polymorphisms on the CVD include patients with PAD and CAD. Subject and Methods: This case control study consisted of 180 subjects were divided into 100 patients with CVD (50 patients with PAD and 50 patients with CAD), and 80 healthy controls. Serum levels for lipid profile and PON1 enzyme were measured by spectrophotometer using paraoxon as a substrate. The genetic polymorphism of PON1 was detected by TaqMan-based allele discrimination RT-PCR Results: The means ±SEM of serum PON1 activity were highly significantly decreased in PAD and CAD as compared to control group. The heterozygote (Q192R) genotype of PON1 polymorphism is abundant among all of the studied groups (68%for PAD, 56% for CAD and 65%for control, respectively) . The CAD patients carry the high risk RR genotyping (odd ratio of 2.69, with the confidence interval of (1.12-6.47; p=0.02).The PAD who carry the RR genotype have a risk ratio 1.57 at confidence interval of 0.61-4.02. Conclusion: Reduction of PON1 activity is one of the risk factor of development of CVD . Patients who carry the RR genotyping were at high risk to develop CVD. Our results indicate that controversial relationships regarding the PON1 rs 662 (Q192R) polymorphism and CVD. Serum PON1 activity is more informative than the PON1 genotype in evaluating the severity and extent of cardiovascular disease in Iraqi patients.