OBJECTIVE - Health of African Americans is seriously threatened by unremitting epidemics of diabetes and cardiovascular disease (CVD). However, the role of metabolic syndrome in the African-American population has not been investigated widely. This study examined the prevalence of metabolic syndrome and assessed its cross-sectional relationship to CVD in the Jackson Heart Study (JHS) cohort. RESEARCH DESIGN AND METHODS - A total of 5,302 participants aged ≥21 years who were recruited at baseline during 2000-2004 were analyzed for this study. Adjusted odds ratios (ORs) were estimated in a logistic regression analysis for coronary heart disease (CHD) and cerebrovascular disease (CBD) in those with and without coexisting metabolic syndrome. Diabetic participants were excluded. RESULTS - Among those aged 35-84 years, metabolic syndrome prevalence was 43.3% in women and 32.7% in men. Elevated blood pressure (70.4%), abdominal obesity (64.6%), and low HDL cholesterol (37.2%) were highly prevalent among those with metabolic syndrome. Prevalence rates for CVD, CHD, and CBD were 12.8, 8.7, and 5.8%, respectively. After adjustment for age and sex, metabolic syndrome was associated with increased age- and sex-adjusted ORs for CVD (OR 1.7 [95% CI 1.4-2.1]), CHD (1.7 [1.4-2.2]), and CBD (1.7 [1.3-2.3]) compared with those without CVD, CHD, or CBD. CONCLUSION - Metabolic syndrome prevalence in the J HS is among the highest reported for population-based cohorts worldwide and is significantly associated with increased ORs for CVD, CHD, and CBD. Abdominal obesity, increased blood pressure, and low HDL cholesterol (without triglyceride elevation) are surprisingly prominent. A high prevalence of low HDL emerges as a leading contributor to metabolic syndrome among African Americans in this large African-American cohort.