Isolated minor nonspecific ST-segment and T-wave abnormalities (NSSTAs), minor and major electrocardiographic (ECG) abnormalities are established, independent risk markers for incident cardiovascular events. Their association with subclinical atherosclerosis has been postulated but is not clearly defined. The aim of this study was to define the association between ECG abnormalities and measurements of subclinical atherosclerosis. We studied participants from MESA, a multiethnic sample of men and women 45 to 84 years of age and free of clinical cardiovascular disease at enrollment. Baseline examination included measurement of traditional risk factors, 12-lead electrocardiograms at rest, coronary artery calcium (CAC) measurement, and common carotid intima-media thickness (CC-IMT). Electrocardiograms were coded using Novacode criteria and were defined as having minor abnormalities (e.g., minor NSSTTAs, first-degree atrioventricular block, and QRS-axis deviations) or major abnormalities (e.g., pathologic Q waves, major STTAs, significant dysrhythmias, and conduction system delays). Multivariable logistic and linear regressions were used to determine cross-sectional associations of ECG abnormalities with CAC and CC-IMT. Of 6,710 participants, 52.7% were women, with a mean age of 62 years. After multivariable adjustment, isolated minor STTAs and minor and major ECG abnormalities were not associated with presence of CAC (>0) in men (odds ratio 1.04, 95% confidence interval 0.81 to 1.33; 1.10, 0.91 to 1.32; and 1.03, 0.81 to 1.31, respectively) or women (1.01, 0.82 to 1.24; 1.04, 0.87 to 1.23; and 0.94, 0.73 to 1.22, respectively). Lack of association remained consistent when using log CAC and CC-IMT as continuous variables. In conclusion, ECG abnormalities are not associated with markers of subclinical atherosclerosis in a large multiethnic cohort.