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Introduction: Acute ischemic stroke (AIS) is common in patients with infective endocarditis (IE). Use of IV thrombolytic therapy (IV-tPA) has been reported and appears to carry greater risk of hemorrhage, while reports of endovascular therapy are rare. We present two cases where these interventions were utilized.Methods: A retrospective review was done of 116 consecutive patients with IE who were seen by stroke neurology in a tertiary care center from January 2015 to July 2016. Two cases were identified in which acute stroke therapy was utilized, one case with IV-tPA and one case with endovascular thrombectomy. We searched PubMed from inception to August 2016 and systematic review was performed to evaluate acute stroke therapy in IE.Results: In case 1, an 82 year old female with prosthetic aortic valve endocarditis and atrial fibrillation presented with slurred speech and right hemiplegia. IV-tPA was given within 2.5 hours, and NIHSS improved from 11 to 1 over 24 hours. CT Brain done 24 hours post-tPA revealed a small L thalamic hemorrhage. In case 2, a 49 year old IV drug-using male with prior IE and current prosthetic aortic valve endocarditis developed right middle cerebral artery occlusion with an NIHSS 17. Endovascular thrombectomy was performed with successful TICI 3 recanalization. CT Brain done 24 hours post-thrombectomy showed evolving right middle cerebral artery infarct with hemorrhagic conversion. Systematic review revealed 7 reports of IV thrombolysis, 5 reports of mechanical thrombectomy, and 3 reports with intra-arterial thrombolysis plus endovascular thrombectomy. Including our cases, IV thrombolysis alone had a hemorrhagic complication rate of 82% (9 out of 11 patients). Endovascular thrombectomy alone, all reporting at least TICI IIb recanalization, had a hemorrhagic complication rate of 17% (1 out of 6 patients). Intra-arterial thrombolysis and endovascular thrombectomy together had a hemorrhagic complication rate of 0% (0 out of 3 patients).Conclusion: Endovascular thrombectomy alone appears to be safer than IV-tPA alone in the management of AIS in patients with IE.