Introduction: A well-documented complication of administering tissue plasminogen activator (tPA) in stroke patients is acute intracranial bleeding. A lesser known but still significant complication is angioedema secondary to tPA administration, which can develop in certain individuals with risk factors such as angiotensin converting enzyme (ACE) inhibitor use and location of the stroke. Knowing the potential for this life-threatening complication and being prepared for its proper management is vital for emergency physicians. Case Report: We report a 53-year-old Black female who presented to the emergency department with sudden onset of slurred speech and a facial droop. She was found to have an acute ischemic stroke and tPA was administered. She subsequently developed angioedema. Retrospectively, the patient was found to have risk factors that are thought to predispose patients to tPA-induced angioedema. Conclusion: Risk factors associated with angioedema secondary to tPA administration have been documented in patients taking ACE inhibitors, as well as patients who develop strokes in the frontal lobe. While many cases may be mild, some patients may develop life-threatening angioedema. Although this complication does not necessarily contraindicate tPA use, it is prudent for the emergency physician to be vigilant for its development, prepared for its treatment, and to be diligent in assessing the need for control of the patient’s airway.

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