Spinal epidural hematoma is a rare complication of thrombolytic therapy (only 9 cases described in the literature). We report the case of a 59-year-old female with hypertension, admitted to the coronary care unit for acute inferior myocardial infarction and treated with tissue-type plasminogen activator 100 mg in 90 min, intravenous heparin 25,000 U, aspirin 100 mg, and metoprolol 50 mg orally once daily. On the third day she suffered from sudden and violent dorsal pain, followed 22 hours later by paraplegia. Magnetic resonance imaging showed a large posterior spinal epidural hematoma, with compression and anterior dislocation of the spinal cord. The patient underwent neurosurgery. After 1 year, she still cannot walk. In patients treated with thrombolytic therapy and presenting with sudden and violent spinal pain, the physician should take into consideration the diagnosis of epidural hemorrhage. Early neurosurgery can save the patient and facilitate neurological recovery.