PURPOSE: To determine the cost-effectiveness of carotid angioplasty with stent placement (CAS) under emboli protection versus carotid endarterectomy (CEA) in patients with severe carotid stenosis considered to be at high surgical risk for CEA. METHODS: The probabilities of various outcomes were adopted from the SAPPHIRE trial results. The quality-adjusted life year (QALYs) associated with each treatment modality were estimated by using the frequencies of various quality-adjusted outcomes (QALY weights of ipsilateral stroke, myocardial infarction, and death). Total cost associated with each intervention was computed using the frequency of stroke, myocardial infarction, and death in each group. Costs are expressed in 2006 US$. Incremental cost-effectiveness ratios (ICERs) were estimated for a 1-year postprocedure period. RESULTS: The mean (range) estimated net costs at 1 year for patients treated with CAS and CEA were $12,782 ($12,205-$13,563) and $8,916 ($8,267-$9,766), respectively. Overall QALYs for the CAS and CEA groups were 0.753 and 0.701 [within a range of 0.0 (meaning death) to 0.815 (meaning no adverse events)]. The mean cost per QALY gained for CAS was $16,223 ($15,315-$17,474) and the mean cost per QALY gained for CEA was $12,745 ($11,372-$14,605). The estimated median ICER for CAS versus CEA treatment was $67,891 (-$129,372 to $379,661). CONCLUSION: The proven non-inferiority of CAS versus CEA in high-surgical-risk patients with severe carotid stenosis might provide a marginal benefit that is offset by the higher cost associated with this procedure.