Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and also plays a role in vascular calcification. The objective of this study was to evaluate the relationship between serum OPG levels, and carotid artery intima-media thickness (IMT) and carotid plaque formation in healthy postmenopausal women. We recruited 68 healthy postmenopausal women for the study. Carotid plaque presence and IMT were evaluated by high resolution B-mode ultrasound. IMT was positively correlated with presence of plaque, age, menopause age and OPG, and inversely correlated with Apolipoprotein A1 (Apo A1). Serum OPG level was positively correlated with IMT (r = 0.366; p < 0.003) and age (r = 0.324; p < 0.008), and negatively correlated with Apo A1 (r = -0.481; p < 0.0001). We did not observe any significant relation between plaque occurrence and levels of serum OPG. In regression analysis OPG (p < 0.02) and menopause age (p < 0.05) were independent risk factors for IMT, and age (p < 0.05) and IMT (p < 0.05) were independent risk factors for plaque formation. Although the role of OPG in the vascular biology is poorly understood, our results suggest that elevated levels of serum OPG is associated with IMT and may play a role in the pathogenesis of atherosclerotic disease.