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Introduction: Early recurrent ischemic stroke (ERIS) after IV thrombolytic therapy is rare. Takotsubo cardiomyopathy (TCM), a reversible stress-induced condition, increases the risk of intracardiac thrombi and subsequent stroke. We describe a patient who presented with a mild ischemic stroke but developed early neurological deterioration (END) due to a large vessel occlusion (LVO) within one hour of receiving Tenecteplase (TNK). This LVO was not seen on initial imaging. Transthoracic echocardiogram (TTE) obtained after the second stroke revealed TCM. She had non-specific ECG findings and an elevated troponin before the onset of the second stroke. We propose that this is the first case report documenting ERIS following TNK administration. ERIS was likely due to an unrecognized cardiac thrombus from TCM. Our patient survived with minimal deficits after appropriate therapy. Description: An 84-year-old female presented two and a half hours after the onset of left-sided neurologic deficits with an initial NIHSS of 3. CT head and CTA head/neck were normal. She received TNK. ECG showed normal sinus rhythm with non-specific ST abnormalities. High sensitivity-troponin was elevated to 267. Fifty-five minutes after TNK administration, the patient developed new right-sided neurologic findings, with an NIHSS of 29. Repeat CTA head/neck revealed an acute left M1/M2 occlusion; she underwent aspiration thrombectomy with TICI 3 revascularization. Brain MRI showed acute left temporoparietal infarcts and scattered right-sided infarcts. TTE revealed LVEF of 40–45%, apical akinesis, and no cardiac thrombus. She was discharged with a loop recorder that did not reveal any dysrhythmias. Discussion: Our patient had ERIS from a likely cardioembolic source due to TCM. There is one other case of a patient with END following thrombolysis without associated atrial fibrillation. It is unclear what triggered her TCM, but given her initial cardiac findings, this occurred before the first stroke. Our patient had a good outcome, which is rare. This was due to rapid access to thrombectomy, which has not been described in other cases. Case reports describing END following IV thrombolysis only describe the use of alteplase. This case brings to light the risk of thromboembolism associated with TCM and ERIS following TNK administration.