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Purpose We explored the association between Framingham risk score (FRS) and coronary artery calcium score (CACS) in asymptomatic Korean individuals. Materials and Methods We retrospectively analyzed 2216 participants who underwent routine health screening and CACS using the 64-slice multidetector computed tomography between January 2010 and June 2014. Relationship between CACS and FRS, and factors associated with discrepancy between CACS and FRS were analyzed. Results CACS and FRS were positively correlated (p < 0.0001). However, in 3.7% of participants with low coronary event risk and high CACS, age, male gender, smoker, hypertension, total cholesterol, diabetes mellitus, and body mass index (BMI; ≥ 35) were associated with the discrepancy. In the diagnostic prediction model for discrepancy, the receiver operating characteristic curve including factors associated with FRS, diastolic blood pressure (≥ 75 mm Hg), diabetes mellitus, and BMI (≥ 35) showed that the area under the curve was 0.854 (95% confidence interval, 0.819–0.890), indicating good sensitivity. Conclusion Diabetes mellitus or obesity (BMI ≥ 35) compensate for the weakness of FRS and may be potential indicators for application of CACS in asymptomatic Koreans with low coronary event risk.