OBJECTIVE The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated that the risk of the primary composite outcome of stroke, myocardial infarction (MI), or death did not differ significantly in patients with an average surgical risk undergoing carotid artery stenting (CAS) and those undergoing carotid endarterectomy (CEA). However, the cost associated with CAS may limit its broad applicability. The authors' goal in this paper was to determine the cost-effectiveness of CAS with an embolic-protection device versus CEA in patients with moderate to severe carotid artery stenosis who are at average surgical risk. METHODS The probability of the primary outcome was obtained from the results of the CREST trial. The quality-adjusted life years (QALYs) associated with each treatment modality were estimated by adjusting for the incidence of each quality-adjusted outcome (QALY weights of ipsilateral stroke, MI, death, and postprocedure QALYs). The total cost associated with each intervention was derived from hospitalization cost and cost associated with primary outcomes including stroke, MI, and death in each group. Costs are expressed in US dollars accounting for inflation up to October 2010. Incremental cost-effectiveness ratios (ICERs) were estimated for the 4-year period after the procedure. All values are expressed as means and 95% confidence intervals. RESULTS The estimated net costs for patients after treatment with CAS and CEA after consideration of the primary outcome were $18,335 and $13,276, respectively, from the definitive presimulation analysis. Postsimulation values were $19,210 (range $18,264-$20,156) and $14,080 (range $13,076-$15,084), respectively. Overall, QALYs for the CAS and CEA groups were 0.712 and 0.702, respectively (ranging from 0.0 [death] to 0.815 [no adverse events]). The estimated ICER for CAS versus CEA treatment was $229,429. CONCLUSIONS Although the CREST demonstrated equivalent results with CAS (compared with CEA) in patients at average surgical risk with severe carotid artery stenosis, broad applicability of CAS might be limited by the higher cost associated with this procedure.