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Abstract Coronary artery calcium score (CACS) is a useful method for predicting coronary artery disease in asymptomatic adults. In this study, we investigated the association between prolonged sedentary time and CACS. A cohort study was conducted in 14949 men with negative CACS (CACS = 0) at baseline who were followed up at least once. Sedentary time was categorized into < 7, 7–8, and ≥ 9 h/day. CACS was calculated by cardiac tomography. During 60,112.1 person-years of follow-up, 569 participants developed positive CACS. The multivariable adjusted hazard ratios (95% confidence intervals) for incident positive CACS comparing sedentary times of 7–8 h/day and ≥ 9 h/day to sedentary time of < 7 h/day were 1.25 (0.97–1.62) and 1.28 (1.03–1.59), respectively. This association was more strongly observed in the non-obese group (BMI < 25 kg/m2). In contrast, in the obese group (BMI ≥ 25 kg/m2), there was no significant association between sedentary time and incidence of positive CACS. Prolonged sedentary time was significantly associated with incidence of positive CACS in the study. CACS is also an effective screening tool for predicting future cardiovascular events in asymptomatic patients. Therefore, CACS can be an effective screening method for predicting coronary artery diseases in people with prolonged sedentary time, especially in metabolically healthy people.