for the SMART Study GroupBackground and Purpose-The frequency of asymptomatic carotid artery stenosis (CAS) increases with age from 0.5% in individuals below 50 years of age to 5% to 10% in individuals over 65 years of age in the general population. Its prognostic value has been examined in the general population but less often in patients with clinical manifestations of arterial disease other than retinal or cerebral ischemia. We examined the relationship between asymptomatic CAS and the risk of subsequent events in this specific group of patients. Methods-This study involved 2684 consecutive patients with clinical manifestations of arterial disease or type 2 diabetes mellitus, but without a history of cerebral ischemia, enrolled in the SMART study (Second Manifestations of ARTerial disease). The degree of asymptomatic CAS was assessed with Duplex scanning and defined on the basis of the blood flow velocity patterns at baseline in both carotid arteries. None of the patients underwent carotid endarterectomy or endovascular intervention. During the follow-up period, vascular events (vascular death, ischemic stroke, and myocardial infarction) were documented in detail. Data were analyzed with Cox proportional hazards regression and adjusted for age, gender, and classic vascular risk factors. Results-Asymptomatic CAS of 50% or greater was present in 221 (8%) patients. During a mean follow up of 3.6 years (SDϭ2.3), a first vascular event occurred in 253 patients (9%). The cumulative incidence rate for the composite of subsequent vascular events after 5 years was 12.3% (95% CIϭ10.7 to 13.9), for cerebral infarction 2.2% (95% CIϭ1.4 to 2.8), and for myocardial infarction 8.0% (95% CIϭ6.6 to 9.4). Adjusted for age and gender, asymptomatic CAS of 50% or greater was related to a higher risk of subsequent vascular events (hazard ratioϭ1.5, 95% CIϭ1.1 to 2.1), in particular of vascular death (hazard ratioϭ1.8, 95% CIϭ1.2 to 2.6). After additional adjustment for vascular risk factors, the hazard ratios remained essentially the same. Conclusion-Asymptomatic carotid artery stenosis is an independent predictor of vascular events, especially vascular death, in patients with clinical manifestations of arterial disease or type 2 diabetes but without a history of cerebral ischemia.