OBJECTIVE: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors leading to atherosclerosis and diabetes. Diabetes is associated with both structural and functional abnormalities of the brain. MetS, even before diabetes is diagnosed, may also predispose to cerebral changes, probably through shared mechanisms. We examined the association of MetS with cerebral changes in patients with manifest arterial disease. RESEARCH DESIGN AND METHODS Cross-sectional data on MetS and brain MRI were available in 1,232 participants withmanifest arterial disease (age 58.6610.1 years; 37%MetS). Volumes of brain tissue, ventricles, and white matter hyperintensities (WMH) were obtained by automated segmentation and expressed relative to intracranial volume. Infarcts were distinguished into lacunar and nonlacunar infarcts. RESULTS: The presence of MetS (n = 451) was associated with smaller brain tissue volume (B 20.72% [95% CI 20.97, 20.47]), even in the subgroup of patients without diabetes (B 20.42% [95% CI 20.71, 20.13]). MetS was not associated with an increased occurrence of WMH or cerebral infarcts. Impaired glucose metabolism, abdominal obesity, and elevated triglycerides were individual components associated with smaller brain volume. Obesity and hypertriglyceridemia remained associated with smaller brain volume when patients with diabetes were excluded. Hypertension was associated with an increased occurrence of WMH and infarcts. CONCLUSIONS: In patients with manifest arterial disease, presence of MetS is associated with smaller brain volume, even in patients without diabetes. Screening for MetS and treatment of its individual components, in particular, hyperglycemia, hypertriglyceridemia, and obesity, may prevent progression of cognitive aging in patients with MetS, even in a prediabetic stage.