Elevated concentrations of D-dimers (DDs) in patients with acute ischemic stroke may cause differential diagnostic problems with regard to pulmonary or deep venous thrombosis. The true relationship between plasma DDs and acute ischemic stroke remains uncertain. We studied acute stroke patients admitted to a single acute neurology department with a specialized stroke unit. As part of our clinical protocol, blood samples of each patient had been taken within the first 24 hours after the onset of stroke symptoms and before anticoagulant treatment had been started, to evaluate the coagulation profile. Each patient's medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Univariate and multivariate statistical analyses were performed. A total of 59 patients admitted to our stroke unit between October 2003 and March 2004 with different stroke subtypes according to the TOAST criteria were evaluated to characterize the impact of stroke category on DD concentration. Family members (n = 23) served as controls in this study. Multivariate regression analysis revealed that patients who sustained cardioembolic stroke had significantly higher DD concentrations than controls and patients who sustained transient ischemic attacks. We identified a correlation between plasma DD levels and different acute ischemic stroke subtypes before any stroke treatment was started. Thus DD concentrations may be considered a direct consequence of marked cerebral infarction and may be useful for physicians when making decisions on treatment for acute ischemic stroke.