OBJECTIVES: This study was undertaken to determine whether atherosclerosis of the ascending aorta is a predictor of long-term neurologic events and mortality. BACKGROUND: Atherosclerosis of the thoracic aorta has been recently considered a significant predictor of neurologic events and peripheral embolism, but not of long-term mortality. METHODS: Long-term follow-up (a total of 5,859 person-years) was conducted of 1,957 consecutive patients ≥50 years old who underwent cardiac surgery. Atherosclerosis of the ascending aorta was assessed intraoperatively (epiaortic ultrasound) and patients were divided into four groups according to severity (normal, mild, moderate or severe). Carotid artery disease was evaluated (carotid ultrasound) in 1,467 (75%) patients. Cox proportional-hazards regression analysis was performed to assess the independent effect of predictors on neurologic events and mortality. RESULTS: A total of 491 events occurred in 472 patients (neurologic events 92, all-cause mortality 399). Independent predictors of long-term neurologic events were: hypertension (p = 0.009), ascending aorta atherosclerosis (p = 0.011) and diabetes mellitus (p = 0.015). The independent predictors of mortality were advanced age (p < 0.0001), left ventricular dysfunction (p < 0.0001), ascending aorta atherosclerosis (p < 0.0001), hypertension (p = 0.0001) and diabetes mellitus (p = 0.0002). There was >1.5-fold increase in the incidence of both neurologic events and mortality as the severity of atherosclerosis increased from normal-mild to moderate, and a greater than threefold increase in the incidence of both as the severity of atherosclerosis increased from normal- mild to severe. CONCLUSIONS: Atherosclerosis of the ascending aorta is an independent predictor of long-term neurologic events and mortality. These results provide additional evidence that in addition to being a direct cause of cerebral atheroembolism, an atherosclerotic ascending aorta may be a marker of generalized atherosclerosis and thus of increased morbidity and mortality.