Patients with atrial fibrillation and echocardiographic risk factors have a relevant risk of cerebral embolism. However, there is little knowledge about the long-term fate and the rate of clinical silent cerebral embolism under continued oral anticoagulation. Our aims were to assess the prognosis of patients with atrial fibrillation and determine a high-risk group with an increased risk of cerebral embolism under oral anticoagulation. A total of 173 consecutive patients with persistent or permanent atrial fibrillation and left atrial (LA) thrombi, dense spontaneous echocontrast, reduced LA appendage peak emptying velocities, or a combination of these were included in the study. In all, 169 patients with atrial fibrillation and without echocardiographic risk factors served as control patients. We performed serial and prospective transesophageal echocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 12 months. During the follow-up period 7 (4%) of the patients at high risk had cerebral embolism with neurologic deficits. A total of 4 (2%) patients died because of embolic events and 19 (11%) patients had silent embolism as documented on magnetic resonance imaging. In the control group, 10 (6%) patients had embolic events documented on magnetic resonance imaging; one was clinically apparent. Study patients with an event had more often previous thromboembolism (P < .0001). Patients with persistent or permanent atrial fibrillation and LA thrombi, dense spontaneous echocontrast, or reduced LA appendage peak emptying velocities have an explicitly increased risk of cerebral embolism (17%) despite oral anticoagulation. Previous thromboembolic event is another important predictor for an event.