Intracranial bleeding is an important and dangerous complication associated with thrombolytic therapy for acute ischemic stroke. Spinal hemorrhage has been reported after systemic thrombolysis for various conditions other than acute ischemic stroke. Our patient presented with an acute ischemic stroke and showed significant clinical recovery during intravenous thrombolysis. CT scan of the brain, performed about 6 h later due to neurological deterioration did not reveal any bleeding or a new infarction. However, an acute epidural hematoma was noted on MRI of the cervical spine. She was treated conservatively and showed a satisfactory recovery. We report, probably the first case of spinal epidural hemorrhage after systemic thrombolysis for acute ischemic stroke. Spinal hemorrhage should be considered as a differential diagnosis for neurological worsening after intravenous thrombolysis for acute ischemic stroke, especially when the brain imaging studies do not reveal an appropriate intracranial pathology.