The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the predictors and progression of subclinical cardiovascular disease (CVD), and the relationship of subclinical disease and its’ progression with clinical CVD in a population-based sample of men and women aged 45-84 who had no evidence of clinical CVD at baseline. 6,814 participants who identified themselves as White (38%), African-American (28%), Hispanic (22%), or Chinese (12%) were recruited from six U.S. communities from 2000-2002. Participants were examined for evidence of subclinical atherosclerosis using computed tomography, cardiac MRI, carotid ultrasound, flow-mediated brachial artery dilation, radial artery tonometry, ankle-brachial index measurement, and retinal photography, and, in subsets, carotid MRI, abdominal aortic CT, and other measures. Examinations of selected components were repeated over five subsequent examinations spanning approximately 16 years. Participation of the surviving cohort was 92, 89, 87, 78, and 68 percent at each of the respective follow-up examinations. Cohort members have been contacted every 9-12 months to obtain information on vital status, current residence, major illness or injury, and hospitalizations occurring between contacts to identify clinical CVD events. Cohort retention was 86% at the last completed follow-up ending on August 14, 2020. The wealth of data and biological samples collected since MESA’s inception as well as the potential for new data collection from MESA participants offer vast opportunities for new scientific discoveries. Task Area 2 will leverage data and samples amassed in MESA to address new questions about the development of clinical CVD. A limited examination of the cohort will be conducted during 2021-2023. An estimated 3000 participants will be examined.