Background: Coronary artery calcium (CAC) predicts incident cardiovascular disease (CVD) beyond traditional risk factors. While higher CAC volume is associated with higher CVD risk, higher CAC density is associated with lower CVD risk. Whether risk factors for CAC volume and CAC density are similar or distinct is unknown. We sought to evaluate the independent associations of CVD risk factors with CAC volume an CAC density. Methods: Baseline measurements from 6,814 participants free of clinical CVD were collected for the Multi-Ethnic Study of Atherosclerosis between 2000 and 2002. Participants with no CAC )n=3,416) and missing data were excluded, for a final analytic sample of 3.375 participants. Multivariable linear regression models were used to evaluate independent predictors of CAC density and CAC volume. Conclusions: Whereas most CVD risk factors were associated with higher CAC volume, the same risk factors were assocated with lower CAC density. For example, diabetes was associated with higher natural logarithm (ln) transformed CAC volume (standardized [beta]=0.44 ln-units, p<0.01) but lower CAC density ([beta]=-0.07 Hounsfield unit (Hu) category unit, p<0.01). Relative to Non-Hispanic White, Chinese, African-American, and Hispanic race/ethnicities were associated with lower ln CAC volume ([beta]=-0.62, -0.52, and -0.40 ln-units, respectively, p<0.01 for each), and higher CAC density ([beta]=0.41, 0.18, and 0.21 Hu category units, respectively, p<0.01 for each). CAC density and CAC volume were also differentially associated with race/ethnicity.