The authors sought to determine a cause-specific mortality profile for US neurosurgeons during the period 1979-2005.Neurosurgeons who died during the study period were identified from the Physician Master File database. Using the National Death Index, the reported cause of death was identified for 93.7% of decedents. Standardized mortality ratios were used to compare mortality risk in the study cohort to that of the US population.There was a marked reduction in mortality from virtually all causes in comparison with the control population. This finding is consistent with prior studies of mortality in physicians. The small number of deaths among female neurosurgeons precluded meaningful analysis for this group. Increased mortality risk for male neurosurgeons was seen from leukemia, nervous system disease (particularly Alzheimer disease), and aircraft accidents. Deaths from viral hepatitis and HIV infection, considered to be occupational hazards for surgeons, were less frequent than in the general population. Suicide, drug-related deaths, and alcohol-related deaths were less frequent than in the general population.Neurosurgeons may be at higher risk for death from leukemia, aircraft accidents, and diseases of the nervous system, particularly Alzheimer disease; however, the mortality profile of neurosurgeons is favorable when compared with the general population.