To evaluate the role of transesophageal echocardiography (TEE) in the diagnostic assessment of cardiac sources of embolism in acute ischemic stroke, 94 consecutive patients (44 men and 50 women, aged 22-82 years) with acute ischemic stroke were prospectively studied. Of these, 34 patients had clinical evidence of heart disease. Both transthoracic and transesophageal echocardiograms were recorded on the same day for each patient. Transthoracic echocardiography (TTE) identified a possible cardiac source of embolism in 2 patients (6%) with and in 3 (5%) without clinical heart disease. TEE identified a possible cardiac source of embolism in 21 patients (62%) with and in 18 (30%) without clinical heart disease. TEE was superior to TTE for the detection of a cardiac source of embolism in patients with acute ischemic stroke (41 vs. 5%, p < 0.001). Factors significantly associated with a greater likelihood of such cardiac sources of embolism included left atrial enlargement, atrial fibrillation and a younger age. The yield of TEE in identifying a possible cardiac source of embolism was higher in patients with clinical evidence of heart disease than in those without.