Background Cardiovascular diseases are the leading cause of death in the United States, yet a significant proportion of adults at high risk remain undetected by standard screening practices. Polygenic risk score for coronary artery disease (CAD‐PRS) improves precision in determining the 10‐year risk of atherosclerotic cardiovascular disease but health benefits and health care costs associated with CAD‐PRS are unknown. We examined the cost‐effectiveness of including CAD‐PRS as a risk‐enhancing factor in the pooled cohort equation (PCE)—the standard of care for determining the risk of atherosclerotic cardiovascular disease—versus PCE alone. Methods and Results We applied a Markov model on a cohort of 40‐year‐old individuals with borderline or intermediate 10‐year risk (5% to