Background: Racial and socioeconomic disparities have not been comprehensively investigated in high-risk neuroblastoma (HR NBL). Prior Children’s Oncology Group (COG) investigations have demonstrated population-based disparities in late relapse rates among Black children, and trial-based disparities in relapse and survival among children living in poverty receiving post-consolidation immunotherapy. It is unknown whether these disparities persist in upfront trials for newly diagnosed patients. We leveraged COG data to investigate race, ethnicity, and socioeconomic disparities in a cohort of children with HR NBL treated on upfront clinical trials from 2007-2016. Methods: Retrospective cohort study of children enrolled on upfront COG HR NBL trials ANBL0532, ANBL09P1, and ANBL12P1. Race and ethnicity were the primary exposures categorized as: Black Non-Hispanic (BNH); Hispanic; Other Non-Hispanic (ONH); or White Non-Hispanic (WNH). Poverty was the secondary exposure, defined as household (public insurance only vs others), area (census-defined high-poverty ZIP code with >20% of population living below 100% Federal Poverty Level (FPL) vs <20% below 100% FPL), and rural (Census-defined rurality measures linked to ZIP code). Overall (OS) and event-free (EFS) survival from time of trial enrollment were plotted by Kaplan-Meier methods; associations with race/ethnicity and poverty were evaluated by log-rank tests. Results: Among 696 children, 16% were BNH, 11% Hispanic, 4% ONH, and 69% WNH. One-third (33%) of children were household poverty-exposed, 26% area poverty-exposed, and 15% rural-exposed. Tumor stage and biology did not differ by race/ethnicity or poverty measures. Five-year OS differed significantly by race/ethnicity (47% Hispanic vs. 50% ONH vs. 61% WNH vs. 62% BNH; p=0.047). Five-year OS was inferior among children exposed to household-poverty (53% vs. 63%; p=0.036) and neighborhood-poverty (54% vs. 62%; p=0.050) compared to unexposed children. There was no difference in OS by rurality. Similar directionality in 5-year EFS outcomes by race/ethnicity and poverty were observed without statistical significance. Conclusions: Race/ethnicity and poverty-exposure are associated with inferior OS outcomes among children with HR NBL despite uniform planned treatment on upfront COG trials. Investigation of mechanisms driving these disparities, including disparate early phase trial enrollment are ongoing to inform targeted health equity interventions to improve outcomes.