This study sought to determine if coronary artery calcium (CAC) is associated with incident noncardiovascular disease.CAC is considered a measure of vascular aging, associated with increased risk of cardiovascular and all-cause mortality. The relationship with noncardiovascular disease is not well defined.A total of 6,814 participants from 6 MESA (Multi-Ethnic Study of Atherosclerosis) field centers were followed for a median of 10.2 years. Modified Cox proportional hazards ratios accounting for the competing risk of fatal coronary heart disease were calculated for new diagnoses of cancer, pneumonia, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), deep vein thrombosis/pulmonary embolism, hip fracture, and dementia. Analyses were adjusted for age; sex; race; socioeconomic status; health insurance status; body mass index; physical activity; diet; tobacco use; number of medications used; systolic and diastolic blood pressure; total and high-density lipoprotein cholesterol; antihypertensive, aspirin, and cholesterol medication; and diabetes. The outcome was first incident noncardiovascular disease diagnosis.Compared with those with CAC = 0, those with CAC >400 had an increased hazard of cancer (hazard ratio [HR]: 1.53; 95% confidence interval [CI]: 1.18 to 1.99), CKD (HR: 1.70; 95% CI: 1.21 to 2.39), pneumonia (HR: 1.97; 95% CI: 1.37 to 2.82), COPD (HR: 2.71; 95% CI: 1.60 to 4.57), and hip fracture (HR: 4.29; 95% CI: 1.47 to 12.50). CAC >400 was not associated with dementia or deep vein thrombosis/pulmonary embolism. Those with CAC = 0 had decreased risk of cancer (HR: 0.76; 95% CI: 0.63 to 0.92), CKD (HR: 0.77; 95% CI: 0.60 to 0.98), COPD (HR: 0.61; 95% CI: 0.40 to 0.91), and hip fracture (HR: 0.31; 95% CI: 0.14 to 0.70) compared to those with CAC >0. CAC = 0 was not associated with less pneumonia, dementia, or deep vein thrombosis/pulmonary embolism. The results were attenuated, but remained significant, after removing participants developing interim nonfatal coronary heart disease.Participants with elevated CAC were at increased risk of cancer, CKD, COPD, and hip fractures. Those with CAC = 0 are less likely to develop common age-related comorbid conditions, and represent a unique population of "healthy agers."