Nonrheumatic atrial fibrillation (AF) frequently coexists with other risk factors far cerebral ischemia. This study was originally designed to determine which combinations of clinical and echocardiographic abnormalities were most closely associated with the risk of cerebral ischemic events. Patients with cerebral ischemic events (n = 214) and community-based control subjects (n = 201) underwent transesophageal echocardiography and carotid artery imaging. Adjusted odds ratios (ORs) were determined using multiple logistic regression analysis. Independent risk factors far cerebral ischemia included diabetes, carotid stenosis, aortic sclerosis, left ventricular dysfunction, left ventricular hypertrophy, left atrial (LA) spontaneous contrast, and proximal aortic atheroma. Nonrheumatic AF in combination with LA spontaneous contrast and LA enlargement showed a strong association with cerebral ischemic events (OR33.7 [95% confidence interval 4.53 to 251]). In subjects with sinus rhythm or nonrheumatic AF, LA enlargement was not associated with an increased risk of cerebral ischemic events in the absence of LA spontaneous contrast. However, only 2 patients and 1 control subject had nonrheumatic AF without LA spontaneous contrast or LA enlargement. Therefore, study of a larger number of subjects is required to address the issue of whether nonrheumatic AF itself carries increased risk. The combination of nonrheumatic AF with LA spontaneous contrast is a potent risk factor for cerebral ischemia. Ascertaining the risk factor in nonrheumatic AF requires adequate examination for underlying cardiac, aortic, and carotid vascular disease. Transesophageal echocardiography may contribute to this assessment.