Abstract Disclosure: S. Karki: None. B. Neupane: None. S. Neupane: None. A. Bhandari: None. U. Farooq: None. K. Rajamani: None. Introduction: Admission day (weekend vs. weekday) significantly influences hospital outcomes and mortality in various diseases, with evidence suggesting higher mortality rates associated with weekend admissions. However, the “weekend effect” on adrenal insufficiency remains underexplored in national inpatient samples. Objective of the study:To assess the impact of admission day on mortality rates, hospital stays, costs, and overall outcomes in adrenal insufficiency patients. Methods: A retrospective cohort study encompassing adult patients (age>18 years) was conducted using the National Inpatient Sample (NIS) data spanning from 2017 to 2020. The International Classification of Disease (ICD-10) was used to select codes for diseases and outcomes. STATA was employed for statistical analysis, using multivariate regression analysis to calculate adjusted odds ratios and account for potential confounding variables. Continuous variables were compared using the student t-test, while proportions were compared using the Fisher exact test. The primary outcome was mortality, with secondary outcomes encompassing length of stay (LOS), total hospitalization charges, acute coronary syndrome (ACS), septic shock, pulmonary edema, acute respiratory failure (ARF), mechanical ventilation, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and cerebrovascular accidents (CVA). Results: A total of 150,005 patients diagnosed with adrenal insufficiency were included in the analysis. Patients with adrenal insufficiency were categorized into two groups based on the day of admission: weekend and weekday. Weekend admissions constituted 23.5% of the total cases of adrenal insufficiency, with 35,330 patients. Significant differences in outcomes were observed in septic shock (aOR=1.16, 7.24 % vs. 6.30 %, p=0.007), ARF (aOR=1.23, 11.82% vs. 9.87%, p<0.001), mechanical ventilation (aOR=1.35, 6.29% vs. 4.76%, p<0.001), ARDS (aOR=1.83, 0.57% vs. 0.33%, p=0.003), and AKI (aOR=1.15, 24.74% vs. 22.58%, p<0.001) in weekend vs weekday admissions. However, no significant differences were observed in mortality rates, mean length of hospital stay, total hospital costs, ACS, pulmonary edema, and CVA. Conclusion: Weekend admissions for adrenal insufficiency showed poorer outcomes which prompts further investigation into underlying factors. Insights gained might be helpful for strategic planning at state and national levels, aiding in outcome improvement. Presentation: 6/1/2024