BACKGROUND AND PURPOSE: Because there is no biologic marker offering precise information about stroke etiology, many patients receive a diagnosis of undetermined stroke even after all available diagnostic tests are done, precluding correct treatment. METHODS: To examine the diagnostic value of biochemical markers and echocardiographic parameters to differentiate stroke etiologies, consecutive acute stroke patients were prospectively evaluated. Brain computed tomography, MRI with angiography, transthoracic echocardiography, and other tests were done to identify an etiologic diagnosis according to TOAST(Trial of ORG 10172 in Acute Stroke Treatment) classification. Blood samples were drawn to test selected biomarkers: high sensitive C-reactive protein, D-dimer, brain natriuretic peptide (BNP). RESULTS: Of the 373 ischemic stroke patients (women 44.2%) included, 11.0% were cardioembolic, 26.3% atherothrombotic, 30.8% lacunar, and 31.9% of undetermined origin. High levels of BNP (276.8 짹 277.3 vs. 79.9 짹 144.0 pg/dL, P<0.0001) and D-dimer (0.67 짹 1.06 vs. 0.39 짹 0.65 mg/L, P=0.02) were observed in patients with cardioembolic stroke compared to patients with other causes. Among echocardiographic parameters, the size of left atrium (LA), LA volume, LA volume index were larger in patients with cardioembolic stroke (44.2 짹 8.4 vs. 36.3 짹 6.4 mm, P<0.0001, 67.7 짹 31.2 vs. 36.4 짹 6.4 ml, P<0.0001, 41.5 짹 19.6 vs. 23.4 짹 10.4 ml/m2, P<0.0001, respectively). Left ventricular ejection fraction was lower than patients with other causes (53.6 짹 11.0 vs. 60.9 짹 7.9 %, P<0.0001). CONCLUSIONS: Using a combination of biomarkers and echocardiographic data may be a feasible strategy to improve the diagnosis of cardioembolic stroke in the acute phase, thus rapidly guiding other diagnostic tests and accelerating the start of optimal secondary prevention.