Atrial fibrillation is associated with an increased risk of peripheral thromboembolism. Although emboli arising from the left atrium are the most probable causes of peripheral ischemic events, coexistent vascular mechanisms may play a role in the genesis of thromboembolism. To assess the prevalence and the relative role of cardiac and vascular sources of thromboembolism in patients with atrial fibrillation 101 consecutive patients with (group 1: 47 patients) and without (group 2: 54 patients) recent thromboembolism were studied by transesophageal echocardiography and ultrasound duplex scanning of carotid arteries. Left atrial thrombosis was found in 19 (40%) group 1 patients and in 3 (5%) group 2 patients. Left atrial thrombosis and/or spontaneous echocardiographic contrast were significantly more frequent in group 1 patients than in group 2 (70% vs 20%, p < 0.001). Stepwise regression analysis revealed that they were the only independent predictors of thromboembolism (p = 0.018, p = 0.0003 respectively). Among clinical and transthoracic echocardiographic variables, left atrial diameter (p = 0.022), rheumatic mitral stenosis (p = 0.0058) and absence of significant mitral regurgitation (p = 0.027) emerged as independent predictors of left atrial thrombosis and/or spontaneous echocardiographic contrast. When transesophageal parameters were also entered into the analysis, the only independent predictor was low blood flow velocity within the left atrial appendage (p = 0.0001). Vascular sources (obstructive carotid arteries plaques, non-obstructive ulcerated carotid plaques and thoracic aortic atherosclerotic debris) were found in 30.6% of patients. Their prevalence was not significantly different in the two groups (34% in group 1, 27% in group 2). Vascular and cardiac sources coexisted in 23% of patients with thromboembolism. Seven of the 10 patients with more severe vascular lesions (i.e., obstructive carotid artery lesions or pedunculated mobile aortic debris) were from group 1 and 5 of them had negative cardiac results. In conclusion, these results indicate that a cardioembolic mechanism due to blood stasis within the left atrium is involved in most of the atrial fibrillation-related thromboembolic events. In patients with atrial fibrillation vascular sources are not infrequent and may be involved in the genesis of ischemic events in some patients. Transesophageal echocardiography may be useful in identifying subgroups of patients with atrial fibrillation who are at high thromboembolic risk.