Background: Oxidative stress is the result of enhanced production of reactive oxygen species (ROS), which are the key molecules in the signaling pathways implicated in vascular inflammation in atherogenesis, starting from the initiation of fatty streak formation to lesion progression and plaque rupture. ROS are established to damage the fundamental biomolecules in cells including DNA, proteins and lipids. Objective: To evaluate the relationship between plasma levels of 8-isoprostaglandin F2-alpha as a marker of oxidative status and the severity of coronary artery disease (CAD) whether or not accompanied with hypertension and/or dyslipidemia. Patients and Methods: This study was carried out from October 2020 to October 2021 at Medical Biochemistry Department, Faculty of Medicine, Al-Azhar University, Cardiac Department in Al-Azhar University Hospital, Egyptian National Heart Institute, Cardiac Department of Police Hospital and Cardiac Department of Minia University Hospital, on one hundred and twenty-five subjects. Results: There was high statistically significant difference between the studied groups as regard systolic BP, diastolic BP and mean arterial pressure blood (MAPB). There was high statistically significant difference between studied groups as regard TC, LDL and triglycerides (TAG). There was high statistically significant difference between studied groups as regard 8-Isoprostane and blood vitamin C. There was high statistically significant difference between studied groups as regard coronary artery disease (CAD) severity. Conclusion: Oxidative stress may play an important role in the pathogenesis of CAD. A high 8-isoPGF2α is a strong and independent risk factor for presence of CAD.