Although nonneurologic organ dysfunction (NNOD) has been shown to significantly affect mortality in subarachnoid hemorrhage, the contribution of NNOD to mortality after severe traumatic brain injury (TBI) has yet to be defined. We hypothesized that NNOD has a significant impact on mortality after severe TBI. The trauma registry was queried for all patients admitted between January 2004 and December 2004 who died during their initial hospitalization after severe TBI (head Abbreviated Injury Score 3 or greater). Cause of death and contributing factors to mortality were determined by an attending trauma surgeon from the medical record. The data were analyzed using both Fisher's exact and Wilcoxon rank sum. One hundred thirty-five patients met inclusion criteria. Sixty-seven per cent were males, 83 per cent were white, and the mean age was 38.5 years. Mean length of stay was 2.9 days. Fifty-four patients (40%) had isolated TBI (chest Abbreviated Injury Score = 0, abdominal Abbreviated Injury Score = 0). Of the 81 deaths attributed to a single cause, 48 (60%) patients died from nonsurvivable TBI or brain death, whereas 33 (40%) died of a nonneurologic cause. Cardiovascular and respiratory dysfunction (excluding pneumonia) contributed to mortality in 51.1 per cent and 34.1 per cent of patients, respectively. NNOD contributes to approximately two-thirds of all deaths after severe TBI. These complications occur early and are seen even among those with isolated head injuries. These findings demonstrate the impact of the extracranial manifestations of severe TBI on overall mortality and highlight potential areas for future intervention and research.