It has been reported that there is a high correlation between fluorodeoxyglucose (FDG) uptake in the aorta and macrophage content of atherosclerotic lesions in an experimental rabbit model. We evaluated the frequency of FDG uptake in the large arteries in relation to the atherogenic risk factors. We also investigated whether FDG uptake of the large arteries is related to clinically known coronary artery disease. The presence of FDG uptake was assessed in the abdominal aorta (AA), iliac (IA), and proximal femoral arteries (FAs) in 156 patients. Medical history of the atherogenic risk factors (age, cigarette smoking, hypertension, diabetes, high cholesterol, and obesity) and coronary artery disease (CAD) was identified for each patient. The frequency of vascular FDG uptake was compared between the patients without risk factors (Group I, 23 patients) and those with at least 1 risk factor (Group II, 133 patients). The correlation of each risk factor and known CAD with arterial FDG uptake was also assessed in the 3 different arteries. There was a significant difference in the frequency of FDG uptake between the 2 groups for the FA (22% vs 70%) and IA (30% vs 54%), but not for the AA (35% vs 53%). Among all risk factors, age was the most significant and consistent factor correlating with FDG uptake in all 3 arteries. Hypercholesterolemia also correlated consistently with FDG uptake in all 3 arteries. The correlation between the remaining risk factors and arterial FDG uptake was rather artery specific than consistent throughout all 3 arteries. A higher frequency of FDG uptake in the FA was seen in patients with CAD compared with those without CAD. Not all risk factors correlated with FDG uptake in different arteries. Among the risk factors, age and hypercholesterolemia most consistently correlated with FDG uptake in the AA, and the IA and proximal FAs. The positive correlation of arterial FDG uptake with the atherogenic risk factors suggested a promising role for FDG-PET imaging in the diagnosis of atherosclerosis and follow-up after treatment intervention.