BACKGROUND: Despite many patients undergoing carotid endarterectomy (CEA) being on dual antiplatelet therapy (DAPT) for cardiac or neurologic indications, the impact of such therapy on perioperative outcomes remains unclear. We aim to compare rates of postoperative bleeding, stroke and major adverse events (stroke, death or MI) among patients on Aspirin alone (ASAA) versus DAPT (Clopidogrel and Aspirin). METHODS: Patients undergoing CEA for carotid artery stenosis between 2010 and 2021 in the Vascular Quality Initiative (VQI) were included. We excluded patients undergoing concomitant or re-do operations or patients with missing antiplatelet information. Propensity score matching was performed between the 2 groups ASAA and DAPT based on age, sex, race, presenting symptoms, major comorbidities [hypertension, diabetes and coronary artery disease (CAD)], degree of ipsilateral stenosis, presence of contralateral occlusion, as well as preoperative medications. Intergroup differences between the treatment groups and differences in perioperative outcomes were tested with the McNemars test for categorical variables and paired t-test or Wilcoxon matched-pairs signed-rank test for continuous variables where appropriate. Relative risks with 95% confidence intervals were estimated as the ratio of the probability of the outcome event in the patients treated within each treatment group. RESULTS: A total of 125,469 patients were included [ASAA n = 82,920 (66%) and DAPT n = 42,549 (34%)]. Patients on DAPT were more likely to be symptomatic, had higher rates of CAD, prior percutaneous coronary intervention or coronary artery bypass grafting, and higher rates of diabetes. After propensity score matching, the DAPT group had an increased rate of bleeding complications (RR: 1.6: 1.4-1.8, P < 0.001) as compared with those on ASAA despite being more likely to receive both drains and protamine. In addition, patients on DAPT had a slight decrease in the risk of in-hospital stroke as compared with patients on ASAA (RR: 0.80: 0.7-0.9, P = 0.001). CONCLUSIONS: This large multi-institutional study demonstrates a modest decrease in the risk of in-hospital stroke for patients on DAPT undergoing CEA as compared with those on ASAA. This small benefit is at the expense of a significant increase in the risk of perioperative bleeding events incurred by those on DAPT at the time of CEA. This analysis suggests avoiding DAPT when possible, during CEA.