Objective Despite the established guidelines, there is not a clear consensus about how to manage antiplatelet therapy after carotid surgery. It is a common practice in vascular surgery to use the combination of aspirin and clopidogrel in the treatment of such patients. In this work, we analyzed the impact on long-term survival of antiplatelet therapy in patients treated for carotid stenosis at a single institution over a 10-year period. Methods Outcomes of 471 patients who underwent carotid intervention (1999-2008) were analyzed. Discharge prescription summaries were retrieved, and patients were divided into two groups according to their antiplatelet regimen: aspirin-only group and aspirin plus clopidogrel group. Only patients with a minimum of 30 days of confirmed antiplatelet therapy were included. All-cause mortality during follow-up represented the primary outcome, whereas stroke and bleeding at 30 days and during follow-up represented secondary end points. When local records were sparse, the Social Security Death Index was queried to confirm mortality. The International Classification of Diseases, 9th Revision (ICD-9 codes), was reviewed for treatment related to a bleeding condition. Results When divided by indication, there was an increased mortality rate in patients with asymptomatic carotid disease receiving dual antiplatelet therapy as compared with aspirin alone (47% vs 40%; P =.05). Patients with symptomatic carotid disease had a nonsignificant decrease in all-cause mortality if they received dual antiplatelet therapy (38% vs 39%; P =.53). In a subgroup analysis, there was a significant increase in the rate of all-cause mortality among patients older than 75 years receiving dual antiplatelet therapy for asymptomatic carotid disease (82% vs 56%; P =.001), whereas there was a nonsignificant decrease in mortality in patients older than 75 years receiving dual antiplatelet therapy for symptomatic carotid disease (47% vs 63%; P =.50). There was no difference in secondary outcomes (stroke and bleeding) regardless of the indication or the antiplatelet therapy. Conclusions In this retrospective, single-institution study, the use of dual antiplatelet therapy (aspirin plus clopidogrel) in patients intervened for asymptomatic carotid disease was related to increased all-cause mortality, whereas it did not significantly influence the outcome in patients with symptomatic carotid disease. © 2014 by the Society for Vascular Surgery.