Objective. The aim of this study was to assess health-related quality of life and self-esteem in adult burn survivors in Brazil. Materials and Methods. This multicenter, cross-sectional analytical study was conducted with 30 adult burn survivors (56.7% were male), 6-24 months postburn, recruited from 3 outpatient burn clinics in the city of São Paulo, Brazil. Half of the burn injuries (50%) were caused by flammable liquids. The mean burn size was 21% of total body surface area. The Short Form 36 Health Survey (SF-36) and the Rosenberg Self-Esteem Scale/Escola Paulista de Medicina at the Federal University of São Paulo were used to assess health-related quality of life and self-esteem, respectively. Statistical analysis was performed using Student’s t test, analysis of variance (ANOVA), Tukey’s test, Kruskal-Wallis test, Dunn’s multiple comparison test, and Spearman’s correlation coefficient. Results. The results showed men reported significantly higher SF-36 scores on the role of emotional (P = 0.023) and mental health (P = 0.047) domains when compared with women. Individuals who abused alcohol had lower scores on bodily pain (P = 0.025), vitality (P = 0.041), mental health (P = 0.023), and self-esteem scores (P = 0.044) compared with nondrinkers, and illicit drug users reported lower bodily pain scores (P = 0.008) compared with nonusers. Conclusion. Women, alcohol abusers, and drug users reported the lowest health-related quality of life and self-esteem among survivors of burn injuries. The assessment of health-related quality of life and self-esteem may contribute to the planning of interventions aimed to minimize the impact of burns on the daily life of this population.