A link between certain infectious microorganisms and an increased risk of atherosclerotic disease has been suggested. By analyzing the data of subjects who had undergone general health-screening tests, a possible association between carotid atherosclerosis and seropositivity of antibody against hepatitis C virus (HCV) has been previously reported. In the present study, a possible link between carotid atherosclerosis and HCV core protein positivity was assessed, because it is postulated to be a better marker of viremia and thus persistent infection. Of the 1992 enrolled subjects, 496 (25%) had carotid artery plaque, and 25 (1.3%) were positive for HCV core protein. Carotid artery plaque was positive in 480/1967 (24%) and 16/25 (64%) of the core protein-negative and core protein-positive subjects, respectively (p<0.0001 by χ² test). Serum concentrations of transaminases were higher in core protein-positive subjects, but albumin concentrations were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that HCV core protein positivity is an independent predictor of carotid plaque with an odds ratio of 5.61 (95% confidence interval 2.06-15.26, p<0.001). These data further support the possible link between persistent HCV infection and carotid atherosclerosis in the subjects without severe liver dysfunction. (Circ J 2003; 67: 26 - 30)