Although the role of transesophageal echocardiography (TEE) in the investigation of stroke mechanism is well established, the value of this test in patients with lacunar presentation is unclear. Review of 214 patients with acute cerebral ischemia referred for TEE to exclude cardioaortic sources of embolism after non-diagnostic basic work-up including carotid ultrasound and transthoracic echocardiography. TEE was considered positive when it showed large or complex aortic arch plaques, left atrial thrombus, mitral or aortic valve vegetations, or patent foramen ovale with atrial septal aneurysm. Multivariate regression analysis was performed to assess the value of lacunar syndrome and radiological small subcortical infarctions in predicting TEE result. Predictive values and likelihood ratios for these variables were calculated. Fifty-two patients (24%) had positive TEE. The most common embolic source was large or complex aortic plaques in 19% of patients. Neither clinical presentation with lacunar syndrome nor the presence of small subcortical infarction on CT scan predicted a negative TEE result on univariate or multivariate analysis. However, the combination of lacunar syndrome with radiological small subcortical infarction was uniformly associated with negative TEE (P = 0.01; negative predictive value 100%). The combination of lacunar syndrome with small subcortical radiological infarct predicts the absence of cardioaortic sources of embolism on TEE in patients with acute cerebral ischemia.