Background and Purpose - Metabolic syndrome (MetSyn) represents a constellation of lipid and nonlipid risk factors for cardiovascular disease and is a recognized target for increased behavioral therapy. Objective - The association between acute ischemic/nonembolic stroke and the MetSyn in elderly individuals was assessed in a population-based case-control study in the prefecture of Ioannina, Greece. Study Population - A total of 163 patients aged older than 70 years admitted with first-ever-in-a-lifetime acute ischemic/nonembolic stroke and 166 controls were included. Results - The prevalence of MetSyn ( defined according to NCEP/ATP III criteria) was high in stroke patients ( 46.0% versus 15.7%, P < 0.001). Compared with controls as a group ( with and without MetSyn), stroke patients with the MetSyn showed higher concentrations of triglycerides, lipoprotein( a), uric acid, and fibrinogen, and lower high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I levels. In logistic regression analysis, crude and adjusted odd ratios (ORs) for MetSyn were 5.33 ( 95% confidence interval [CI], 2.91 to 9.79; P < 0.0001) and 2.59 ( 95% CI, 1.24 to 5.42; P = 0.012), respectively. The analysis of interaction between MetSyn and its individual components revealed significant associations with abdominal obesity ( adjusted OR, 2.74; 95% CI, 1.15 to 6.50; P = 0.02), hypertension ( OR, 2.03; 95% CI, 0.91 to 4.49; P = 0.08), high fasting glucose levels ( OR, 2.95; 95% CI, 1.19 to 7.35; P = 0.02), high triglyceride ( OR, 5.55; 95% CI, 2.71 to 11.37; P < 0.0001]), and low HDL cholesterol ( OR, 5.42; 95% CI, 2.85 to 10.30; P < 0.0001). Notably, in stroke patients with the MetSyn the inverse relationship between HDL cholesterol levels and ischemic stroke was negated ( OR, 1.04; 95% CI, 1.02 to 1.05; P < 0.0001). Conclusions - MetSyn is associated with an increased risk for acute ischemic/nonembolic stroke in elderly subjects with significant contributions from its individual components. In the presence of MetSyn, HDL cholesterol loses its protective role against ischemic stroke.