Introduction: Hospitalized pediatric hematology-oncology (PHO) patients have frequent clinical deterioration events (CDE) requiring Intensive Care Unit (ICU) interventions and resulting in high mortality, particularly in resource-limited settings. The objective of this study is to describe patterns and risk factors for CDE mortality in hospitalized PHO patients in Latin America. Methods: In 2017, we implemented a prospective CDE registry among centers participating in a quality improvement collaborative in Latin America (Proyecto EVAT), with CDE defined as unplanned transfer to a higher level-of-care, use of ICU-level interventions on the floor, or non-palliative floor death. This study analyzes registry data between April 2017 and December 2022. CDEs mortality was defined as death occurring during ICU admission or within 24 hours of ICU discharge or end of ward-based ICU interventions. All CDEs with a mortality outcome (yes/no) were included in analysis. Wilcoxon rank-sum test and Chi-square tests were used to identify potential risk factors for CDE mortality. Results: Among 69 centers in 18 countries, 4,142 CDEs were reported in PHO patients (range 3-405/center) with an event mortality of 26% (1,095 events, range 0-43%/center); 368 (33.6% of deaths) occurred within 24 hours of event start. Of all CDEs, 34% (1,394 events) used ICU interventions on the ward, 15% (613 events) experienced a ward cardiopulmonary arrest, and 87% (3,622 events) were transferred to a higher level-of-care. Significant risk factors for event mortality present at the start of deterioration included oncologic diagnosis, relapsed oncologic disease, using ICU interventions on the ward, high lactate, thrombocytopenia, neutropenia, high CRP, number of organs with dysfunction, septic shock, high PIM2, perceived delay in ICU transfer, and lack of ICU bed availability. Country income-level was not related to mortality, however, mortality varied across hospital type, financing, PHO unit structure, and PHO volume. Conclusions: Hospitalized PHO patients with CDE in resource-limited settings frequently require ward-based ICU interventions and have high mortality, with significant variability across centers. Targeted interventions are urgently needed to improve outcomes in these high-risk patients.