Although laboratory studies indicate that female rodents better tolerate the deleterious consequences of trauma and have higher survival rates than male rodents, it remains unclear whether a similar gender dimorphic pattern is evident in humans. In view of this, the association between gender and mortality in trauma patients admitted to a University Level I Trauma Center was assessed. All adult patients admitted to the University of Alabama at Birmingham Trauma Center with blunt or penetrating injury between July 1996 and March 2001 were selected for analysis. Patients were categorized by mechanism (blunt or penetrating), and odds ratios (ORs) were used to compare the risk of death among males compared with females. The ORs were stratified according to age and were adjusted for demographic, medical, and injury characteristics. Male blunt trauma patients <50 years old had a 2.5 times (95% CI 1.3–4.9) higher risk of death than females; however, for those ≥50 years old, a smaller, nonstatistically significant difference was apparent (OR 1.4, 95% CI 0.8–2.3). Conversely, for penetrating trauma, males <50 years old exhibited an increased yet nonsignificant risk of death (OR 1.8, 95% CI 0.6–5.4), whereas those ≥50 years old had a survival advantage (OR 0.1, 95% CI 0.02–0.5). Laboratory studies have demonstrated that estrogens are salutary and androgens are detrimental for survival following trauma-hemorrhage. The results of this study suggest that the physiologic pattern of premenopausal adult female sex hormones may provide a survival advantage in blunt trauma patients; however, the converse pattern prevails for the penetrating trauma patients.