Background: Influenza causes greater morbidity in pediatric patients with cancer or sickle cell disease (SCD). Limited data exists on influenza vaccination uptake for these populations in a low-vaccination state. Outpatient interventions improve vaccine uptake but isolated inpatient interventions remain unstudied. Procedure: We reviewed influenza vaccination of pediatric patients with cancer or SCD treated at Children’s Healthcare of Atlanta (CHOA) during three influenza seasons. An opt-out inpatient admission order set was implemented prior to the 2019-2020 influenza season. Vaccination status of patients that were admitted during an influenza season was compared pre- and post-intervention via Chi-squared analysis and multivariate logistic regression. Results: 1548 and 2549 patients with cancer and SCD (respectively) were eligible. The oncology (60%-62%) and SCD cohorts (61%-65%) had similar-to-higher vaccination uptake to the US (58-64%, p=0.01-0.79) and higher uptake compared to Georgia (51%-56%, p<0.01). There was no significant improvement in uptake after implementation of the inpatient intervention for admitted patients with cancer (40% vs 56%, p=0.05-0.88) or SCD (44% vs 56%, p=0.01). Multivariate logistic regression also found no significant increase in vaccine uptake (Hematologic Malignancy: 0.8 [0.73-0.98], Solid Tumor: 0.9 [0.80-1.90], CNS Tumor: 0.9 [0.71-1.14], SCD: 0.9 [0.85-0.99]). Conclusion: Pediatric patients with cancer and SCD have similar-to-greater influenza vaccination uptake compared to Georgia and the United States. An intervention focused on vaccinating hospitalized patients did not significantly improve the proportion of cancer or SCD patients who received influenza vaccine in each season. Future studies are needed to identify alternative approaches to improving vaccine uptake in these cohorts.