Background and Purpose-More than 47 million individuals in the United States meet the criteria for the metabolic syndrome. The relation between the metabolic syndrome and stroke risk in multiethnic populations has not been well characterized. Methods-As part of the Northern Manhattan Study, 3298 stroke-free community residents were prospectively followed up for a mean of 6.4 years. The metabolic syndrome was defined according to guidelines established by the National Cholesterol Education Program Adult Treatment Panel III. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs for ischemic stroke and vascular events (ischemic stroke, myocardial infarction, or vascular death). The etiologic fraction estimates the proportion of events attributable to the metabolic syndrome. Results-More than 44% of the cohort had the metabolic syndrome (48% of women vs 38% of men, PϽ0.0001), which was more prevalent among Hispanics (50%) than whites (39%) or blacks (37%). The metabolic syndrome was associated with increased risk of stroke (HRϭ1.5; 95% CI, 1.1 to 2.2) and vascular events (HRϭ1.6; 95% CI, 1.3 to 2.0) after adjustment for sociodemographic and risk factors. The effect of the metabolic syndrome on stroke risk was greater among women (HRϭ2.0; 95% CI, 1.3 to 3.1) than men (HRϭ1.1; 95% CI, 0.6 to 1.9) and among Hispanics (HRϭ2.0; 95% CI, 1.2 to 3.4) compared with blacks and whites. The etiologic fraction estimates suggest that elimination of the metabolic syndrome would result in a 19% reduction in overall stroke, a 30% reduction of stroke in women; and a 35% reduction of stroke among Hispanics. Conclusions-The metabolic syndrome is an important risk factor for ischemic stroke, with differential effects by sex and race/ethnicity. (Stroke. 2008;39:30-35.)