BACKGROUND: The safety and efficacy of carotid endarterectomy (CEA) in stroke prevention has been well documented. But "high-risk" patients have traditionally been excluded from these studies and may be offered alternate therapies. We examined the safety of CEA in veterans, a medically high-risk group with multiple comorbidities. STUDY DESIGN: The records of all patients having CEAs performed between 1995 and 1999 in the Connecticut Veterans Affairs (VA) hospital were reviewed. Survival and freedom from stroke were determined using Kaplan-Meier survival analysis. The effects of risk factors on outcomes were analyzed with Cox regression. RESULTS: There were 128 CEAs performed in 120 patients, with a mean followup of 8.5 years. Most patients were symptomatic preoperatively and had a high incidence of hypertension (830/6), coronary artery disease (64%), diabetes (37%), and pulmonary disease (22%). Incidences of perioperative (30-day) mortality (0.8%), stroke (1.6%), and myocardial infarction (0.8%) were low. Survival rates at 8.9 and 12 years were 50% and 13%, respectively, with 90% patient fellowup. Freedom from ipsilateral stroke was 90% at 12 years. Age (hazards ratio [H R] 1.1, p = 0.004), hypertension (HR 2.6, p = 0.04), and elevated creatinine (HR 3.7, p = 0.001) were significant risk factors for mortality. Age (HR 0.8, p = 0.07) and diastolic blood pressure (HR 1.2, p = 0.06) were predictive of ipsilateral stroke. CONCLUSIONS: Despite poor health and symptomatic presentation, patients treated with CEA achieved excellent perioperative Outcomes and were protected from stroke for the remainder of their lives. Multiple medical comorbidities should not be used as exclusion criteria for CEA.