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Introduction: Most acute ischemic stroke (AIS) patients post cardiac catheterization are excluded from intravenous thrombolysis therapy because of prolonged PTT from heparin during the procedure. The outcome of these patients are unfavorable with high mortality.Method: Case report and literature review.Results: An 87-year-old man with diabetes mellitus, hypertension, neurofibromatosis, and hyperlipidemia underwent an elective trans-radial cardiac catheterization for abnormal stress test evaluation. He had 2 drug-eluting stents for severe stenosis of mid circumflex and right coronary arteries. He received heparin 13,000 IU during procedure. He developed acute left hemiparesis with initial NIH stroke scale (NIHSS) of 4. CT brain and CT angiogram of head and neck were unremarkable. Bedside activated clotting time (ACT) was 181. Protamine 40 mg was administered and ACT levels were at 138 when it was repeated after 30 minutes.Intravenous tissue plasminogen activator (IV tPA) was administered at 4 hours 25 minutes from his last known well. Within 15 minutes, his NIHSS was 0. Brain MRI showed no acute infarction 24 hours post stroke. To our knowledge, Only 5 AIS cases post cardiac catheterization received protamine prior IV-tPA administration. Three cases received only 0.6 mg/kg of IV- tPA dose. The mean initial NIHSS was 10 (range: 4-16) and mean discharge NIHSS was 1 (range: 0-2). They all have favorable outcomes and no intracranial hemorrhage were reported.Conclusion: Protamine reversal of heparin for AIS post cardiac catheterization seems to be safe. Further studies are needed to confirm the therapeutic safety and efficacy of this strategy.