Introduction: Tissue plasminogen activator (tPA), commonly used for treatment of acute ischemic stroke, is associated with life-threatening bleeding intracranially as well as surrounding the airway. 

Case Report: A 78-year-old year old male who presented with stroke symptoms and after tPA administration developed a retropharyngeal hematoma requiring intubation and surgical intervention. 

Conclusion: Numerous threats to the patient’s airway can develop after tPA administration. While angioedema is the most common cause, it is important to be prepared for other causes related to hemorrhage.