The importance of gender differences in quality of life and psychologic morbidity after major trauma is a newly recognized focus of trauma outcomes research. The Trauma Recovery Project is a large, prospective, epidemiologic study designed to examine multiple outcomes after major trauma, including quality of life (QoL), and psychologic sequelae such as depression and early symptoms of acute stress reaction (SASR). The specific objectives of the present report are to examine gender differences in QoL outcomes and the early incidence of combined depression and SASR after injury, controlling for injury severity, specific body area injured, and mechanism. Between December 1, 1993, and September 1, 1996, 1,048 eligible trauma patients triaged to four participating trauma center hospitals in the San Diego Regionalized Trauma System were enrolled in the study. The enrollment criteria for the study included age 18 years and older, admission Glasgow Coma Scale score of 12 or greater, and length of stay greater than 24 hours. QoL outcome after trauma was measured after injury using the Quality of Well-being scale, a sensitive index to the well end of the functioning continuum (range, 0 = death to 1.000 = optimum functioning). Depression was assessed using the Center for Epidemiologic Studies scale. SASR was assessed using the Impact of Events scale. Patient outcomes were assessed at discharge and at 6, 12, and 18 months after discharge. Women (n = 313) were significantly more likely to have poor QoL outcomes at follow-up than men (n = 735) (women vs. men: 12-month follow-up odds ratio [OR] = 2.2, p < 0.001; 18-month follow-up OR = 2.0, p < 0.001). Quality of Well-being scores at each of the 6-, 12-, and 18-month follow-up time points were markedly and significantly lower in women compared with men, independent of injury severity, serious and moderate injury status, lower extremity injury, intentional or unintentional injury type, and blunt or penetrating injury. Women were also significantly more likely to develop early combined depression and SASR at discharge (OR = 1.7, p < 0.01) and to have continuous depression throughout the 18-month follow-up period (OR = 2.3, p < 0.001). These analyses provide further important and more detailed evidence that women are at risk of worse QoL outcomes and early psychologic morbidity after major trauma than men, independent of mechanism and injury severity. A better understanding of the impact of major trauma in men and women will be an important component of efforts to improve trauma care and long-term outcome in mature trauma systems.