Objective: The purpose of this systematic review and meta-analysis was to synthesize the available evidence derived from randomized controlled trials (RCTs) regarding the relative efficacy and safety of endarterectomy vs stenting in patients with carotid artery disease. Methods: We searched MEDLINE, EMBASE, Current Contents, and Cochrane CENTRAL through July 2010 to update previous systematic reviews. Two reviewers determined trial eligibility and extracted descriptive, methodologic, and outcome data (death, nonfatal stroke, and nonfatal myocardial infarction). Random-effects meta-analysis was used to pool relative risks and the I2 statistic was used to assess heterogeneity. Results: Thirteen RCTs proved eligible enrolling 7484 patients, of which 80% had symptomatic disease. Methodological quality was moderate to high, with better quality among RCTs published after 2008. Compared with carotid endarterectomy, stenting was associated with increased risk of any stroke (relative risk [RR], 1.45; 95% confidence interval [CI], 1.06-1.99; I 2 = 40%), decreased risk of periprocedural myocardial infarction (MI; RR, 0.43; 95% CI, 0.26- 0.71; I2 = 0%), and nonsignificant increase in mortality (RR, 1.40; 95% CI, 0.85-2.33; I2 = 5%). When analysis was restricted to the two most recent trials with the better methodology and more contemporary technique, we found stenting to be associated with a significant increase in the risk of any stroke (RR, 1.82; 95% CI, 1.35-2.45) and mortality (RR, 2.53; 95% CI, 1.27-5.08) and a nonsignificant reduction of the risk of MI (RR, 0.39; 95% CI, 0.12-1.23). For every 1000 patients opting for stenting rather than endarterectomy, 19 more patients would have strokes and 10 fewer would have MIs. Outcome data in asymptomatic patients were sparse and imprecise; hence, these conclusions apply primarily to symptomatic patients. Conclusion: Compared with endarterectomy, carotid artery stenting (CAS) significantly increases the risk of any stroke and decreases the risk of MI. © 2011 Society for Vascular Surgery.