<b><i>Background:</i></b> Current guidelines for the primary prevention of atherosclerotic cardiovascular disease are based on the estimation of a predicted 10-year cardiovascular disease risk and the average relative risk reduction estimates from statin trials. In the clinical setting, however, decision-making is better informed by the expected benefit for the individual patient, which is typically lacking. Consequently, a personalized statin benefit approach based on absolute risk reduction over 10 years (ARR<sub>10</sub> benefit threshold ≥2.3%) has been proposed as a novel approach. However, how this benefit threshold relates with coronary plaque burden in asymptomatic individuals with low/intermediate cardiovascular disease risk is unknown. <b><i>Aims:</i></b> In this study, we compared the predicted ARR<sub>10</sub> obtained in each individual with plaque burden detected by coronary computed tomography angiography. <b><i>Methods and Results:</i></b> Plaque burden (segment volume score, segment stenosis score, and segment involvement score) was assessed in prospectively recruited asymptomatic subjects (<i>n</i> = 70; 52% male; median age 56 years [interquartile range 51–64 years]) with low/intermediate Framingham risk score (< 20%). The expected ARR<sub>10</sub> with statin in the entire cohort was 2.7% (1.5–4.6%) with a corresponding number needed to treat over 10 years of 36 (22–63). In subjects with an ARR<sub>10</sub> benefit threshold ≥2.3% (vs. < 2.3%), plaque burden was significantly higher (<i>p</i> = 0.02). <b><i>Conclusion:</i></b> These findings suggest that individuals with higher coronary plaque burden are more likely to get greater benefit from statin therapy even among asymptomatic individuals with low cardiovascular risk
