Clinical and experimental studies have shown a decreased mortality for women after nonthermal injury. However, recently published data from this institution showed an increased mortality for female patients younger than 60 years of age with thermal injury. This study extended these observations to evaluate outcomes related to sex in thermal injury in a larger population of patients. The National Burn Repository (NBR) was used for this analysis. Patients admitted to burn centers between 1991 and 2001 were selected for inclusion (n = 49,079). Sex differences in demographic, injury, clinical, and outcome characteristics were compared. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between mortality and sex, both overall and stratified by age. In total, 34,470 men and 14,609 women were included in this study. Women had a 50% increased risk of death when compared with men (OR 1.5; 95% CI 1.3–1.6), which diminished slightly when adjustments were made for age, race, TBSA burn, and inhalation injury (OR 1.3; 95% CI 1.2–1.5). When stratified by age, women had an increased risk of death for all age groups between 10 and 70 years. This study confirmed earlier studies showing an association between sex and burn mortality. Further prospective studies analyzing differences in immune responses between men and women after burn injury may provide insight into the mechanism behind these divergent outcomes and identify targets for future therapy.