OBJECTIVE: The safety of carotid endarterectomy in patients with a response to antiplatelet agents (aspirin and clopidogrel) confirmed by point-of-care testing is unknown. Thus, we sought to determine whether using point-of-care assessment of platelet inhibition reveals risk factors for operative complications or predicts clinical outcomes. METHODS: We reviewed records of carotid endarterectomy patients treated from March 2013 to July 2015 to extract demographics, lesion characteristics, laboratory data, procedural complications, and follow-up. Administration of aspirin, clopidogrel, or therapeutic anticoagulation within 5 days before surgery was recorded. RESULTS: We analyzed 79 patients with 86 lesions (mean age 70.9 +/- 10.0 years). More patients with a P2Y(12) reaction unit (PRU) <170 had neck hematomas (4/10, 40.0%) than those with a PRU >= 170 (2/9, 22.2%) (P = 0.63). Estimated blood loss >= 100 mL was more frequent among patients with PRU <170 (9/10, 90.0%) than among those with PRU >= 170 (5/9, 55.6%) (P = 0.09). Clopidogrel use, regardless of response, independently predicted neck hematoma in a logistic regression model, with increased odds of 8.5. Mean postoperative modified Rankin Scale scores did not differ statistically between clopidogrel users and nonusers at a mean followup of 108.5 +/- 146.3 days (P = 0.27). CONCLUSIONS: Clopidogrel use within 5 days of carotid endarterectomy independently predicted postoperative neck hematomas, most of which were managed conservatively. Patients with PRU < 170 were more likely to have estimated blood loss >= 100 mL during surgery and surgery lasting >= 3 hours.