Background and Purpose-The outcomes of carotid endarterectomy (CEA) are, in addition to patient baseline characteristics, highly dependent on the safety of the surgical procedure. During the successive stages of the operation, transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) was used to assess the association of cerebral microembolism and hemodynamic changes with stroke and stroke-related death. Methods-By use of data pooled from 2 hospitals in the United States and the Netherlands, including 1058 patients who underwent CEA, the association of various TCD emboli and velocity variables with operative stroke and stroke-related death was evaluated by univariable and multivariable logistic regression analyses in combination with receiver operating characteristic (ROC) curve analyses. The impact of basic patient characteristics, such as age, sex, preoperative cerebral symptoms, and ipsilateral and contralateral internal carotid artery stenosis, on the prediction of operative stroke was also evaluated. Results-We observed 31 patients with ischemic and 8 patients with hemorrhagic operative strokes. Four of these patients died. Emboli during dissection (odds ratio [OR] 1.5, 95% CI 0.8 to 2.9) and wound closure (OR 2.3, 95% CI 1.2 to 4.4) as well as greater than or equal to 90% decrease of MCA peak systolic velocity at cross-clamping (OR 3.3, 95% CI 1.3 to 8.5) and greater than or equal to 100% increase of the pulsatility index of the Doppler signal at clamp release (OR 7.1, 95% CI 1.4 to 35.7) were independently associated with stroke. The ROC area of this model was 0.69. Of the patient characteristics, only preoperative cerebral ischemia (OR 1.9, 95% CI 1.0 to 3.7) and greater than or equal to 70% ipsilateral internal carotid artery stenosis (OR 0.5, 95% CI 0.2 to 0.9) were associated with stroke. Adding these patient characteristics to the model, the area under the ROC curve increased to 0.73. Conclusions-In CEA, TCD-detected microemboli during dissection and wound closure, greater than or equal to 90% MCA velocity decrease at cross-clamping, and greater than or equal to 100% pulsatility index increase at clamp release are associated with operative stroke. In combination with the presence of preoperative cerebral symptoms and greater than or equal to 70% ipsilateral internal carotid artery stenosis, these 4 TCD monitoring variables reasonably discriminate between patients with and without operative stroke. This supports the use of TCD as a potential intraoperative monitoring modality to alter the surgical technique by enhancing a decrease of the risk of stroke during or immediately after the operation.