Basic research and our previous studies have suggested that mercury exposure enhances lipid peroxidation and the risk of myocardial infarction, but there are no studies concerning the association between mercury accumulation and atherosclerosis. We therefore investigated whether high hair mercury content is associated with accelerated progression of carotid atherosclerosis, determined by ultrasonographic assessment of common carotid intima-media thickness (IMT), in a prospective study among 1014 men aged 42–60 years. In a linear regression model adjusting for other atherosclerotic risk factors, high hair mercury content was one of the strongest predictors of the 4-year increase in the mean IMT (P=0.0007). On the average, for each μg/g increase in hair mercury content, there was an increment of 8 μm (7.3% of the mean) in the 4-year IMT increase. Men with hair mercury content of <0.49, 0.49–0.91, 0.92–1.49, 1.50–2.81 and >2.81 μg/g (fifths) had an IMT increase of 0.105, 0.102, 0.113, 0.107 and 0.140 mm/4 years, respectively (P=0.041 for heterogeneity between groups). The IMT increase was 0.034 mm/4 years (31.9%) greater in the highest fifth than in the other fifths (P<0.05 for the difference). These findings suggest that mercury accumulation in the human body is associated with accelerated progression of carotid atherosclerosis.