Background. The level of circulating P53 is related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether P53 is associated with the severity of atherosclerosis remains to be determined. Hypothesis: This study examines the relationship of systemic P53 levels with atherosclerotic risk factors and subclinical atherosclerosis. Methods: Circulating levels of P53 and markers of inflammation were measured in 356 subjects with cardiovascular risk factors but who were free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima-media thickness (IMT) and the presence of atherosclerotic plaques with the use of B-mode ultrasound in all subjects. Results: P53 levels were positively correlated with age (r = 0.382, P < 0.001), intercellular adhesion molecular-1 (ICAM-1; r = 0.510, P < 0.01), vascular cell adhesion molecular-1 (VCAM-1; r = 0.497, P < 0.01), E-selectin (r = 0.337, P < 0.01), and carotid IMT (r = 0.594, P < 0.01). The association between P53 and IMT remained significant in multiple regression analysis (P < 0.01) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Conclusion: Higher plasma P53 levels were associated with an increase in inflammatory markers, as well as increased carotid IMT. Circulating P53 may be useful in identifying subclinical atherosclerosis in subjects symptomatically free from cardiovascular disease.