Although abnormal lipoproteins and lipoprotein ratios are powerful risk factors for clinical cardiovascular events, these associations are stronger in younger than in older subjects. Whether age modifies the relation of lipoproteins and lipoprotein ratios to the relative risk of subclinical cardiovascular disease (CVD), as assessed by coronary artery calcium (CAC) scores, has not been examined in a contemporary, multiethnic cohort. We performed multivariate relative risk regression analyses to determine the relative risks for associations of lipoproteins and lipoprotein ratios with prevalent CAC in participants in Multi-Ethnic Study of Atherosclerosis (MESA). The participants were community-dwelling adults aged 45 to 84 years without clinically apparent CVD at baseline. We excluded those taking lipid-lowering therapy (15%) and stratified the results by decades of age. A total of 5,092 participants met the inclusion criteria. In the fully adjusted models, per SD of low-density lipoprotein, the age-stratified, adjusted relative risk for CAC was 1.17 (95% confidence interval [CI] 1.07 to 1.28) for those aged 45 to 84 years but was 1.05 (95% CI 1.01 to 1.10) for those aged 75 to 84 years (p-interaction = 0.12). The relative risk per SD of total/high-density lipoprotein cholesterol ratio was 1.20 (95% CI 1.12 to 1.29) for those aged 45 to 54 years but only 1.04 (95% CI 1.00 to 1.09) for those aged 75 to 84 years (p-interaction <0.001). The lipoproteins levels and lipoprotein ratios were associated with increased relative risks for CAC across all age categories. However, these associations were markedly attenuated by age. In conclusion, abnormal lipoprotein levels in middle age are a powerful risk factor for early atherosclerosis, as manifested by prevalent CAC.