OBJECTIVES: To evaluate mortality in adolescents and young adult patients with chronic diseases followed in a Latin American tertiary hospital. METHODS: A cross-sectional retrospective study was performed in a tertiary/academic hospital in the state of São Paulo, Brazil. Death occurred in 529/2850 (18.5%) adolescents and young adult patients with chronic diseases, and 25/529 (4.7%) were excluded due to incomplete medical charts. Therefore, 504 deaths were evaluated. RESULTS: Deaths occurred in 316/504 (63%) of early adolescent patients and in 188/504 (37%) of late adolescent/young adult patients. Further comparisons between early adolescents (n=316) and late adolescent/young adult patients (n=188) with pediatric chronic diseases at the last hospitalization showed that the median disease duration (22.0 [0-173] vs. 43.0 [0-227] months, p<0.001) was significantly lower in early adolescents vs. late adolescent/young adult patients. The median number of previous hospitalizations was significantly lower in the former group (4.0 [1-45] vs. 6.0 [1-52], p<0.001), whereas the last hospitalization in intensive care unit was significantly higher (60% vs. 47%, p=0.003). Regarding supportive measures, palliative care was significantly lower in the younger group compared to the older group (33% vs. 43%, p=0.02). The frequencies of renal replacement therapy (22% vs. 13%, p=0.02), vasoactive agents (65% vs. 54%, p=0.01), and transfusion of blood products (75% vs. 66%, p=0.03) were significantly higher in the younger group. The five most important etiologies of pediatric chronic diseases were: neoplasias (54.2%), hepatic diseases/transplantation (10%), human immunodeficiency virus (5.9%), and childhood-onset systemic lupus erythematosus and juvenile idiopathic arthritis (4.9%). Autopsy was performed in 58/504 (11%), and discordance between clinical and postmortem diagnoses was evidenced in 24/58 (41.3%). CONCLUSIONS: Almost 20% of deaths occurred in adolescents and young adults with distinct supportive care and severe disease patterns. Discordance between clinical diagnosis and autopsy was frequently observed.