Objective: In medically high-risk patients the choice between carotid artery stenting (CAS) and carotid endarterectomy (CEA) can be difficult. The purpose of this study was to compare risk-stratified outcomes of CAS and CEA. Methods: Patients who underwent isolated primary CEA (n = 11,336) or primary CAS (n = 544) at 29 centers in the Vascular Study Group of New England were analyzed (2003-2013); patients with previous ipsilateral CEA or CAS, or concomitant coronary artery bypass graft were excluded. A medical risk score based on predicted 5-year mortality was developed for each patient using a Cox proportional hazards model. Patients in the highest risk score quartile were termed high-risk (vs normal-risk for the other three quartiles). Medically high-risk patients had a 5-year survival of 65% and comprised 23% of CEA and 25% of CAS patients. Risk-stratified outcomes were compared within neurologically symptomatic and asymptomatic patients. Results: Among asymptomatic patients, rates of in-hospital stroke and/or death were not different between CAS and CEA in normal and high-risk cohorts, ranging from 0.7% in normal-risk CEA patients to 1.6% in high-risk CAS patients. In symptomatic patients, significantly worse outcomes were seen with CAS compared with CEA in normal-risk and high-risk patients. Normal-risk symptomatic patients had a stroke or death rate of 1.3% with CEA, but 5.2% with CAS (P < .01). In high-risk symptomatic patients, the stroke or death rate was 1.5% with CEA and 9.3% with CAS (P < .01). No significant differences were seen between asymptomatic CEA and CAS within risk strata across secondary outcome measures of stroke, death, or myocardial infarction, and ipsilateral stroke, major stroke, or death. However, symptomatic high-risk CAS patients had significantly greater rates of all secondary outcomes compared with CEA except death, and symptomatic normal-risk CAS patients had only significantly greater rates of death and stroke, death, or myocardial infarction. Conclusions: In the Vascular Study Group of New England, asymptomatic normal- and high-risk patients do equally well after CEA or CAS. However, normal- and high-risk symptomatic patients have substantially worse outcomes with CAS compared with CEA. High medical risk alone might be an insufficient indication for CAS in symptomatic patients.