OBJECTIVE The impact of extracranial carotid stenosis on interventional revascularization of acute anterior circulation stroke is unknown. The authors examined the effects of high-grade carotid stenosis on the results of endovascular treatment of patients in the Interventional Management of Stroke (IMS)-III trial. METHODS The 278 patients in the endovascular arm of the IMS-III trial were categorized according to the degree of carotid stenosis as determined by angiography. In comparing patients with severe stenosis or occlusion (≥ 70%) to those without severe stenosis (< 70%), the authors evaluated the time to endovascular reperfusion, modified Thrombolysis in Cerebrovascular Infarction (mTICI) scores, 24-hour mean infarct volumes, symptomatic intracerebral hemorrhage rates, and modified Rankin Scale (mRS) scores at 90 days. RESULTS Compared with the 249 patients with less than 70% stenosis, patients with severe stenosis (n = 29) were found to have a significantly longer mean time to reperfusion (105.7 vs 77.7 minutes, p = 0.004); differences in mTICI scores, infarct volumes, hemorrhage rates, and mRS scores at 90 days did not reach statistical significance. Multiple regression analysis revealed that severe carotid stenosis (p < 0.0001) and higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.004) were associated with an increase in time to reperfusion. Older age (p < 0.0001), higher NIHSS score (p < 0.0001), and the absence of reperfusion (p = 0.001) were associated with worse clinical outcomes. CONCLUSIONS Severe ipsilateral ICA stenosis was associated with a significantly longer time to reperfusion in the IMS-III trial. Although these findings may not translate directly to modern devices, this 28-minute delay in reperfusion has significant implications, raising concern over the treatment of tandem ICA stenosis and downstream large-vessel occlusion.