The decrease in cardiovascular death rates in the United States has been slower in blacks than whites, especially in patients <65 years of age. The Dallas Heart Study was designed as a single-site, multiethnic, population-based probability sample to (1) produce unbiased population estimates of biologic and social variables that pinpoint ethnic differences in cardiovascular health at the community level and (2) support hypothesis-driven research on the mechanisms causing these differences using genetics, advanced imaging modalities, social sciences, and clinical research center methods. A probability-based sample of Dallas County residents aged 18 to 65 years was surveyed with an extensive household health interview. The subset of participants 30 to 65 years of age provided in-home fasting blood and urine samples and underwent multiple imaging studies, including cardiac magnetic resonance imaging and electron beam computed tomography. Completed interviews were obtained for 6,101 subjects (54% black), phlebotomy visits for 3,398 (52% black), and clinic visits for 2,971 (50% black). Participation rates were 80.4% for interviews, 75.1% for phlebotomy visits, and 87.4% for clinic visits. Weighted population estimates of many measured variables agreed closely with those of the United States census and were relatively stable from the interview sample to the phlebotomy and clinic subsamples. Thus, the Dallas Heart Study provides a phenotypically well-characterized probability sample for multidisciplinary research that will be used to improve the mechanistic understanding and prevention of cardiovascular disease, especially in black Americans.