In carotid endarterectomy (CEA) patients, platelet aggregation is increased despite heparinization. We investigated whether this phenomenon correlates with the occurrence of perioperative microemboli. Of 27 CEA patients, 18 (67%) used aspirin and 9 also used clopidogrel. Blood was collected at multiple time points before, during, and after CEA. Platelet aggregation and P-selectin expression were determined. Transcranial Doppler monitoring was used to measure microemboli. Platelet aggregation showed a significant increase 5 minutes postheparinization compared with preheparinization (19.7 +/- 2.8% vs 8.9 +/- 0.9% in the aspirin group and 22.5 +/- 4.4% vs 8.7 +/- 1.2% in the clopidogrel group; p < .01 and p < .05, respectively). P-selectin expression showed a tendency to increase postheparinization in both groups (p = .07 and p = .09, respectively). The number of microemboli ranged from 0 to 50. Clopidogrel patients displayed fewer microemboli than aspirin patients (4.1 +/- 2.3 vs 17.6 +/- 18.2; p < .01). Patients with a high number of microemboli displayed had a tendency toward higher baseline platelet aggregation than patients with a low number of microemboli (p = .08). In conclusion, platelet aggregation is transiently increased during CEA despite the administration of antiplatelet agents. Clopidogrel is associated with a decreased number of perioperative microemboli. The exact relationships between these findings, postoperative microemboli formation, and the risk for thromboembolic complications after CEA remain to be determined.