Posterior spinal fusion with instrumentation is a routine elective treatment of lumbar stenosis with radiculopathy and myelopathy. Fat embolism syndrome (FES) is a rare complication of this procedure. We describe the first documented case of fatal FES after an L3-L5 posterior spinal fusion using off-label bone morphogenic protein 2 (BMP-2) and allograft instead of iliac crest bone grafting. Postoperatively, the patient developed delayed cerebral symptoms with swift respiratory failure and cardiac arrest. Based on our investigation, it is likely that pedicle screw fixation was the cause of the fat embolisms with little effect from BMP-2.