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Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, was associated with subclinical atherosclerosis in many cross-sectional studies, but the prospective association between NAFLD and the progression of atherosclerosis has not been evaluated. This study was conducted to evaluate the association between NAFLD and the progression of coronary atherosclerosis.This retrospective cohort study included 4731 adult men and women with no history of cardiovascular disease (CVD), liver disease or cancer at baseline who participated in a repeated regular health screening examination between 2004 and 2013. Fatty liver was diagnosed by ultrasound based on standard criteria, including parenchymal brightness, liver-to-kidney contrast, deep beam attenuation and bright vessel walls. Progression of coronary artery calcium (CAC) scores was measured using multidetector CT scanners.The average duration of follow-up was 3.9 years. During follow-up, the annual rate of CAC progression in participants with and without NAFLD were 22% (95% CI 20% to 23%) and 17% (16% to 18%), respectively (p0.001). The multivariable ratio of progression rates comparing participants with NAFLD with those without NAFLD was 1.04 (1.02 to 1.05; p0.001). The association between NAFLD and CAC progression was similar in most subgroups analysed, including in participants with CAC 0 and in those with CAC0 at baseline.In this large cohort study of adult men and women with no history of CVD, NAFLD was significantly associated with the development of CAC independent of cardiovascular and metabolic risk factors. NAFLD may play a pathophysiological role in atherosclerosis development and may be useful to identify subjects with a higher risk of subclinical disease progression.