Predominantly, males have a higher risk of injury mortality and morbidity than females. However, less is known about gender differences for injury and trauma outcome at a regional level. The aim of this study was to examine the epidemiologic profile and trauma outcomes of males and females at a level 1 trauma center to inform local injury prevention efforts. A retrospective review was conducted of injuries identified from the trauma registry of the New South Wales St George Public Hospital during January 1, 2004, to December 31, 2008. There were 6763 major trauma presentations, and 65.1% of these were of males. Males had a higher proportion of trauma presentations in each age group, except for those younger than 15 years, 45 to 54 years, and older than 65 years. Almost all presentations were as a result of unintentional injuries. However, 8% of males were victims of assault compared with 2% of females. Males were more likely to be injured while working and during leisure or sports activities and at sporting, farming, home, trade, and industrial locations than females. Males were more likely to be more severely injured than females and generally had a longer hospital length of stay. There was no significant difference in the rate of mortality between the genders. There are distinct differences between the sexes regarding the mechanism and severity of injury and trauma outcomes. Local injury prevention initiatives should be targeted to address gender differences. Future social research should examine the interplay of the construction of masculinities with male injury.