OBJECTIVE AND IMPORTANCE: Intra-arterial thrombolysis has been demonstrated to improve recanalization and outcomes among patients with acute ischemic stroke. However, thrombolytic agents have limited effectiveness and are associated with a significant risk of bleeding. Bivalirudin is a direct thrombin inhibitor that has been demonstrated in the cardiology literature to have a more favorable efficacy and bleeding profile than other antithrombotic medications. We report the use of bivalirudin during endovascular treatment of acute stroke, when hemorrhagic complications are not uncommon. CLINICAL PRESENTATION: A 71-year-old woman with atrial fibrillation presented with right hemiparesis and aphasia and was found to have a National Institutes of Health Stroke Scale score of 10. Computed tomographic scans revealed no evidence of intracranial hemorrhage, aneurysm, or ischemic stroke. Cerebral angiography revealed thromboembolic occlusion of the superior division of the left middle cerebral artery. INTERVENTION: For anticoagulation, a loading dose of bivalirudin was intravenously administered before the interventional procedure, followed by continuous infusion. Attempts to remove the clot with an endovascular snare failed to induce recanalization of the vessel. Bivalirudin was then administered intra-arterially. Immediate postprocedural angiography demonstrated restoration of flow in the left middle cerebral artery. Repeat computed tomographic scans demonstrated no intracranial hemorrhage. The patient's hemiparesis and aphasia were nearly resolved and her National Institutes of Health Stroke Scale score was 2 at the time of her discharge 5 days later. CONCLUSION: To our knowledge, this is the first report of the use of bivalirudin for treatment of acute ischemic stroke. Bivalirudin may be a useful agent for intravenous anticoagulation and intra-arterial thrombolysis in this setting.