Intracerebral hemorrhage is an unusual complication of autonomic hyperreflexia (AHR), which can be fatal if massive bleeding occurs with subsequent brain herniation. Episodes of AHR are most often triggered by bladder and rectal distention. We present a case of a 45-year-old quadriplegic male who suffered left basal ganglia and thalamic hemorrhage associated with AHR during surgery for pressure sore defects in the prone position under local anesthesia. Early recognition and removal of triggering factors of AHR failed to bring his blood pressure under control. The patient continued to deteriorate neurologically and died 9 days after the attack. A preventive measure rather than episodic treatment of AHR may be of paramount importance to avoid life-threatening complications, especially when a patient with a history of AHR is undergoing surgery in the prone position.