BackgroundCoronary artery calcium (CAC) is a predictor for the development of cardiovascular disease (CVD) and to a lesser extent cancer. The age‐ and sex‐specific relationship ofCACwithCVDand cancer mortality is unknown.Methods and ResultsAsymptomatic patients aged 40 to 75 years old without knownCVDwere included from theCACConsortium. We calculated sex‐specific mortality rates per 1000 person‐years’ follow‐up. Using parametric survival regression modeling, we determined the age‐ and sex‐specificCACscore at which the risk of death fromCVDand cancer were equal. Among the 59 502 patients included in this analysis, the mean age was 54.9 (±8.5) years, 34% were women, and 89% were white. There were 671 deaths attributable toCVDand 954 deaths attributable to cancer over a mean follow‐up of 12±3 years. Among patients withCAC=0, cancer was the leading cause of death, the total mortality rate was low (women, 1.8; men, 1.5), and theCVDmortality rate was exceedingly low for women (0.3) and men (0.3). The age‐specificCACscore at which the risk ofCVDand cancer mortality were equal had a U‐shaped relationship for women, while the relationship was exponential for men.ConclusionsThe age‐ and sex‐specific relationship ofCACwithCVDand cancer mortality differed significantly for women and men. Our age‐ and sex‐specificCACscore provides a more precise estimate and further facilitates the use ofCACas a synergistic tool in strategies for the prediction and prevention ofCVDand cancer mortality.