Fetuin-A is a circulating glycoprotein which is well characterized as an inhibitor of ectopic calcification. Vascular calcification commonly found in chronic kidney disease (CKD) patients is a predictor of cardiovascular death. Recently, several groups have demonstrated that low fetuin-A levels are associated with mortality in uraemic patients, possibly through regulation of vascular calcification. However, the physiological significance of fetuin-A in atherosclerosis remains unknown, except in specific conditions, such as vascular calcification in CKD patients. The objective of this study was to investigate the association between serum fetuin-A levels and arterial stiffness, a functional property of atherosclerosis, in healthy subjects. The study subjects comprised 141 healthy subjects. We measured serum fetuin-A levels and stiffness parameter beta for the common carotid artery, which was assessed by ultrasound using a phase-locked echo-tracking system. Simple regression analyses indicated that serum fetuin-A levels were significantly correlated with stiffness parameter beta (r = 0.200, P = 0.018). Multiple regression analyses showed that, besides age, fetuin-A (beta = 0.166, P = 0.033) independently contribute to the stiffness parameter beta (R(2) = 0.310, P < 0.0001). Serum fetuin-A level is associated with carotid arterial stiffness, independent of known atherogenic factors in healthy subjects.