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 ≥ 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 ≥ 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. © 2003 Lippincott Williams and Wilkins, Inc.