The homeless are at an increased risk for traumatic injury, but little is known about the injury etiology and outcome of homeless persons who sustain burn injuries. In this study, we analyze patient and injury characteristics of homeless persons admitted to a regional burn center. This is a retrospective cohort study of patients admitted to our burn center between 1994 and 2005. A total of 3700 adult patients were admitted during the study period and, of these, 72 (1.9%) were homeless. The cohort of homeless patients was compared with domiciled adult patients admitted during the same time period, analyzing baseline patient and injury characteristics and injury outcomes. Overall, homeless patients had more extensive burn injuries than domiciled patients (17.8% vs 11.2%TBSA, P < .001) and overall longer lengths of hospital stay (22 vs 12 days, P < .001). The homeless population also had significantly higher rates of alcohol (80.6% vs 12.8%, P < .001) and drug abuse (59.4% vs 12.8%, P < .001), history of mental illness (45.2% vs 11.0%, P < .001), and injury by assault (13.9% vs 2.0%, P < .001). Homeless patients tended to have more severe injuries; higher rates of substance abuse and mental illness; increased incidence of assault by burning; and longer lengths of hospital stay. Hospitalization of a homeless patient following injury may provide a unique opportunity to address co-occurring substance abuse and mental illness and approach injury prevention to improve patients’ outcomes and reduce injury recidivism.