Introduction Early administration of intramuscular epinephrine can be life-saving in the acute management of anaphylaxis. Rarely, intracranial hemorrhage (ICH) can occur after epinephrine use due to rapid elevations in blood pressure. We report a rare case of a man who developed ICH following epinephrine injection for acute anaphylaxis. Case Description A 70-year-old man with end-stage renal disease on dialysis, hypertension, and diabetes presented to the emergency department with a 1-month history of left ear pain. He had no prior history of anaphylaxis, intracranial hemorrhage, stroke, or allergies. Initial vital signs showed blood pressure of 203/87 mmHg. Physical exam revealed left edematous ear canal and mastoid tenderness, with no focal neurologic deficits. Suspected mastoid infection prompted a CT temporal bone scan with contrast, which was consistent with otomastoiditis and showed no evidence of intracranial hemorrhage or other intracranial pathology. Empiric antibiotic treatment was given with cefepime and vancomycin. Within 10 minutes of initiating vancomycin infusion, he developed shortness of breath and tongue/facial swelling, with blood pressure 152/116 mmHg. The patient then rapidly decompensated, developing altered mental status, bradycardia (30 bpm), hypoxia (40% O2 on pulse oximetry), and minimally palpable pulse. Anaphylaxis was suspected, and 0.3 mg intramuscular epinephrine, diphenhydramine, and dexamethasone were given. A repeat BP 5 minutes later showed hypertension up to 261/102 mmHg. Due to altered mental status and for airway protection, an emergent surgical airway was established with subsequent blood pressure 114/108 mmHg twenty minutes after sedation and ventilation with tracheostomy tube. Patient was subsequently admitted to the intensive care unit. Four days later, MRI brain with/without contrast for evaluation of osteomyelitis showed incidental bilateral intraventricular hemorrhage and acute pontine hemorrhages, confirmed stable by subsequent CT six hours later. Patient had no neurologic deficits and was discharged to a rehabilitation facility 35 days later with a tracheostomy collar. Discussion First-line treatment of anaphylactic shock is administration of epinephrine; however, adverse events can occur. Epinephrine can cause short term elevations in systolic blood pressure. Factors that can cause precipitation of intracranial hemorrhage include platelet dysfunction in the setting of chronic kidney disease with dialysis and hypertensive urgency. Physicians should be aware of ICH as a rare cerebrovascular complication of epinephrine injection in the setting of anaphylaxis, particularly in elderly patients with hypertension and high bleeding risk.