BACKGROUND: Several studies have reported a null association between gender and mortality after traumatic injury, whereas others found an age-specific association between male gender and increased mortality. Relatively small sample sizes may have contributed to the heterogeneity among existing studies; therefore, a large-sample-size study was undertaken. METHODS: The National Trauma Data Bank was queried, yielding data for over 150,000 patients involved in blunt or penetrating trauma. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between gender and mortality, both overall and according to mechanism of injury and age categories. RESULTS: Among those who sustained blunt trauma, male patients had a significant increase in the risk of death compared with female patients (OR, 1.49; 95% CI, 1.39-1.59) that was most apparent for those > or = 50 years of age (OR, 1.97; 95% CI, 1.84-2.11). For penetrating trauma patients, essentially no significant association, either overall (OR, 1.03; 95% CI, 0.91-1.17) or by age category, was apparent. CONCLUSION: This study found an association between gender and mortality among blunt trauma patients, particularly those aged > or = 50 years. Animal studies demonstrate that the sex hormones influence the inflammatory response to injury. These results may highlight the importance of sex hormones in traumatic injury outcomes.