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Few patients presenting with acute ischemic stroke ( AIS) are eligible for alteplase, especially those receiving ongoing anticoagulation. We describe the first reported case of a patient receiving full-dose intravenous ( IV) alteplase for AIS after heparin reversal with protamine. A 73-year-old man presented with AIS. He was treated with IV heparin, tirofiban, loading-dose prasugrel, and aspirin before percutaneous coronary intervention ( PCI) for placement of a right coronary artery stent. One hour following PCI, he abruptly developed left hemiparesis and dysphagia. The National Institutes of Health Stroke Scale was 12, and activated partial thromboplastin time ( aPTT) was longer than 150 seconds. Head computed tomography (CT) showed no acute pathology, and CT angiogram showed no large-vessel occlusion amenable to mechanical thrombectomy. Repeat aPTT, obtained 45 minutes later, was 110 seconds, at which time protamine 40 mg IV was administered. At 144 minutes from last known well time, full-dose IV alteplase (0.9 mg/kg) was administered. Follow-up head imaging at 25 hours showed right pontine and cerebellar AIS with no evidence of hemorrhage. The patient was discharged to inpatient rehabilitation 2 days later. Modified Rankin Scale at 3 months was 3, improved from 5 at discharge. Given the lack of adverse events associated with IV alteplase in our patient, we advocate cautious evaluation for potential reversal of acutely administered anticoagulation to facilitate alteplase administration in severely disabled patients who are not eligible for mechanical intervention and would have been excluded from definitive AIS treatment. [ABSTRACT FROM AUTHOR]