Age is a well-known risk factor in trauma patients. The aim of the present study was to define the age-dependent cut-off for increasing mortality in multiple injured patients. Pre-existing medical conditions in older age and impaired age-dependent physiologic reserve contributing to a worse outcome in multiple injured elderly patients are discussed as reasons for increased mortality. A retrospective clinical study of a statewide trauma data set from 1993 through 2000 included 5375 patients with an Injury Severity Score (ISS) > or = 16 who were stratified by age. The ISS and Abbreviated Injury Score (AIS) quantified the injury severity. Outcome measures were mortality, shock, multiple organ failure, and severe head injury. Mortality in this series increased beginning at age 56 years, and that increase was independent of the ISS. The mortality rate increased from 7.3% (patients 46-55 years of age) to 13.0% (patients ages 56-65 years) in patients with ISS 16-24; from 23.8% to 32.1% in those with ISS 25-50; and from 62.2% to 82.1% in those with ISS 51-75 (P < or = 0.05). Severe traumatic brain injury (sTBI) was the most frequent cause of death, with a significant peak in patients older than 75 years. The incidence of lethal multiple organ failure increased significantly beginning at age 56 years (P < or = 0.05), but it showed no further increase in patients aged 76 years or older. In contrast, the incidence of lethal shock showed a significant increase from age 76 years (P < or = 0.05), but not at age 56 years. However, from age 56 years, mortality increased significantly in patients who sustained multiple trauma-an increase that was independent of trauma severity.