Objectives: To evaluate the cost-effectiveness of carotid stenting vs. carotid endarterectomy using data from the SAPPHIRE trial. Background: Carotid stenting with embolic protection has been introduced as an alternative to carotid endarterectomy for prevention of cerebrovascular and cardiovascular events among patients at increased surgical risk. Methods: Between August 2000 and July 2002, 310 patients with an accepted indication for carotid endarterectomy but at high risk of complications were randomized to and subsequently underwent either carotid stenting (n = 159) or endarterectomy (n = 151). Clinical outcomes, resource use, costs, and quality of life were assessed prospectively for all patients over a 1-year period. Life expectancy, quality-adjusted life expectancy, and health care costs beyond the follow-up period were estimated for patients alive at 1 year, based on observed clinical events during the first year of follow-up. Results: Although initial procedural costs were significantly higher for stenting than for endarterectomy (mean difference: $4,081/patient; 95% CI, $3,849–$4,355), mean post-procedure length of stay was shorter for stenting (1.9 vs. 2.9 days; P < 0.001) with significant associated cost offsets. As a result, initial hospital costs were just $559/patient higher with stenting (95% CI, $3,470 less to $2,289 more). Neither follow-up costs after discharge nor total 1-year costs differed significantly. The incremental cost-effectiveness ratio for stenting compared with endarterectomy was $6,555 per quality-adjusted life year (QALY) gained, with over 98 percent of bootstrap estimates <$50,000/QALY gained. Conclusions: Although carotid stenting with embolic protection is more costly than carotid endarterectomy, by commonly accepted standards, stenting is an economically attractive alternative to endarterectomy for patients at high surgical risk. © 2011 Wiley-Liss, Inc.