Objective: Carotid angioplasty and stenting (CAS) is a percutaneous alternative to carotid endarterectomy (CEA) for treating patients with carotid artery stenosis. This study sought to evaluate whether patients at increased perioperative risk for CEA may be treated with CAS while maintaining equivalent outcomes. Methods: This study was a nonblinded, retrospective analysis of data obtained from September 2002 to present in the CAS group and from January 1997 to present in the CEA group. Two hundred thirty-one CAS and 647 CEA procedures were performed. Patients were selected for CAS based on criteria that placed them at increased risk for standard CEA surgery. Except for percentage women treated, baseline demographics did not differ between patients treated with CAS and CEA: mean age (72.0 years [range 46-94] vs 70.5 years [range 42-92], P = NS), mean follow-up (12.8 ± 11.8 months vs 8.7 ± 10.0 months, P = NS) and percentage women treated (41.4% vs 32.3%, P = .03). Cerebral protection devices were used in 228/231 patients treated with CAS, and each patient underwent an NIH Stroke Scale assessment 24 hours postoperatively and at 30 days follow-up by an independent observer. Results: Preoperative neurologic symptoms did not differ between patients treated with CAS and CEA: amaurosis fugax (6.06% vs 6.96%, P = NS), transient ischemic attacks (13.4% vs 13.9%, P = NS), strokes (19.9% vs 14.1%, P = NS) and total symptoms (27.7% vs 30.5%, P = NS). Due to the selection of patient groups based on predefined clinical characteristics, factors associated with an increased risk of complications from standard CEA surgery were generally more prevalent in patients treated with CAS: neck irradiation (6.06% vs 1.24%, P < .001), neck dissection for cancer therapy (7.8% vs 1.5%, P < .001), prior ipsilateral CEA (15.2% vs 3.4%, P ≤ .001), contralateral carotid artery occlusion (12.1% vs 1.1%, P < .001), modified Goldman Cardiac Risk II-moderate risk (26.0% vs 11.3%, P < .001) and modified Goldman Cardiac Risk III-high risk (16.4% vs 2.1%, P < .001) in patients treated with CAS and CEA, respectively. Perioperative outcomes did not differ between patients treated with CAS and CEA: myocardial infarction (MI) (1.7% vs 2.6%, P = NS), stroke without residual symptoms (1.3% vs 1.2%, P = NS), stroke with residual symptoms (0.4% vs 0.8%, P = NS), mortality (0.4% vs 0.6%, P = NS), and total MI/stroke/mortality rate (3.9% vs 5.3%, P = NS). Conclusions: The data in this study demonstrate that high-risk patients undergoing CAS had comparable outcomes to low-risk patients undergoing CEA. This study supports the use of CAS as a reasonable alternative for patients at increased perioperative risk for CEA.