Background: Neuroblastoma is the most common extracranial solid tumor in children, with about half of cases classified as high risk. Treatment varies by risk level, with high-risk patients undergoing aggressive multimodal therapy. Long-term survival has improved, but survivors face significant risks of late treatment effects, including adrenal insufficiency. This study investigates the incidence of adrenal insufficiency among neuroblastoma patients, focusing on high-risk versus non-high-risk cases. Procedure: This retrospective cohort study at a single tertiary children’s hospital reviewed records from 1998 to 2021, identifying 370 neuroblastoma patients, of which 137 had complete risk stratification. The primary outcome was the incidence of adrenal insufficiency, diagnosed based on clinical evaluation and response to hydrocortisone therapy. Demographic and clinical data were collected, and statistical analyses were performed to compare high-risk and non-high-risk groups. Results: Among 137 neuroblastoma patients, 9 (12.0%) high-risk and 3 (4.9%) non-high-risk patients were diagnosed with adrenal insufficiency. The cumulative incidence of adrenal insufficiency was 16.6% in high-risk and 3.5% in non-high-risk patients. High-risk patients with adrenal insufficiency had a median time of 10.2 months from neuroblastoma diagnosis to adrenal insufficiency diagnosis, with all cases occurring in patients with adrenal primary tumors. There were no significant differences in demographic or clinical characteristics between high-risk patients with and without adrenal insufficiency. Conclusions: The study found a higher cumulative incidence of adrenal insufficiency in high-risk neuroblastoma patients, particularly those with adrenal primary tumors. Despite the lack of significant prevalence difference between risk groups, the findings underscore the need for vigilant monitoring and screening for adrenal insufficiency in neuroblastoma patients during and after treatment. Future research should include larger, multi-institutional cohorts to better understand risk factors and optimize screening protocols.