Angioedema, a swelling of the subcutaneous or submucosal layers of the skin or gastrointestinal tract, is a potential complication to thrombolytic therapy in the treatment of acute ischemic strokes. In these cases, angioedema develops due to increased levels of bradykinin as a result of the activation of the fibrinolytic pathway and contact activation system. Angioedema can involve the tongue, larynx, and vocal cords, leading to occlusion of the airway and death due to asphyxiation. It is vital for the emergency physician to know that this complication can occur to ensure appropriate monitoring for development of angioedema. We report the case of a 65-year-old Black man who presented with signs of an acute ischemic stroke and was treated with tenecteplase. The patient's stroke symptoms mostly resolved within 90 minutes; however, he developed swelling of his right upper lip consistent with angioedema. The patient was treated with steroids and antihistamines. He was closely monitored and did not require airway intervention. The angioedema was almost fully resolved by the following day. Angioedema is a known complication of thrombolytic therapy for acute ischemic stroke. Risk factors for alteplase-associated angioedema include use of angiotensin-converting enzyme inhibitors, female gender, diabetes, and infarcts of the insula and frontal cortex. As hospital systems switch from alteplase to tenecteplase for the treatment of acute ischemic strokes for reasons of cost and ease of administration, it is important to recognize that angioedema is also a potential complication of tenecteplase.