PURPOSE To determine whether carotid stenting with embolic protection is equivalent to carotid endarterectomy (CEA) in a broad risk population of patients with symptomatic and asymptomatic carotid stenosis. METHODS A prospective, multicenter Phase I trial was conducted comparing standard CEA to carotid stenting systems (CSS) in patients with symptomatic (> or =50%) and asymptomatic (> or =75%) carotid stenosis. Patients were enrolled using selection criteria reflective of broad clinical practice. The enrollment ratio at each clinical site was designed to be 2:1 (CEA to CSS) to achieve a planned enrollment of 450 patients: 300 in the CEA arm and 150 in the CSS cohort, which would ensure adequate precision with a coefficient of variation < or =0.35. The primary endpoint for comparison was 30-day all-cause mortality and nonfatal stroke. RESULTS Between April 2001 and December 2002, 14 clinical sites enrolled 439 patients, of which 397 (247 men; mean age 71 years, range 44-89) were treated: 254 with CEA and 143 patients with CSS (ratio 1.8 to 1.0). More than 90% of patients had >75% stenosis; approximately 68% of patients were asymptomatic. There were no significant differences in baseline patient characteristics between the treatment groups with the exception of a more frequent history of prior CEA (30% CSS versus 11% for CEA, p<0.0001) and prior carotid stent placement in the CSS group (6% versus 0% for CEA, p=0.0002). There was no significant difference in the 30-day combined all-cause mortality and stroke rate by Kaplan-Meier estimate between CEA (2%) and CSS (2%). There was no significant difference in the secondary endpoint of combined 30-day all-cause mortality, stroke, and myocardial infarction between CEA (3%) and CSS (2%). CONCLUSIONS This study suggests that the 30-day risk of stroke or death following carotid stenting with cerebral protection is equivalent to standard carotid endarterectomy in a broad risk population of patients with carotid stenosis.