7078 Background: Management of complications of systemic therapy for cancer involves significant healthcare burden for both patients and healthcare system. Aim of this study is to estimate trends as well as burden associated with these hospitalizations, using a nationally representative data. Methods: National Inpatient Sample data during 2005-2016 was used to identify complications of systemic therapy using ICD-9 and ICD-10 external cause of injury codes. Primary outcome was hospitalization rate while secondary outcomes were cost and in-hospital mortality related to these complications. Results: There were 443,222,223 hospitalizations recorded during the study period, of which 2,419,722 were due to complications of systemic therapy. The average annual percentage change of these hospitalizations was 8.1%, compared to -0.5% for general hospitalizations. The 3 most common causes for hospitalization were anemia (12.8%), neutropenia (10.8%), and sepsis (7.8%). During the study period, hospitalization rates had highest relative increases for sepsis (1.9 fold) and acute kidney injury (1.6 fold) and highest relative decrease for dehydration (0.21 fold) and fever of unknown origin (0.35 fold). Complications responsible for highest costs per hospitalization were sepsis ($16,834), acute kidney injury ($13,172), and pneumonia ($13,040). Leading causes of in-hospital mortality associated with systemic therapy were sepsis (15.8%), pneumonia (7.6%), and acute kidney injury (7.0%). Conclusions: During 2005-2016, hospitalization rates for systemic therapy complications increased by an annual rate of 8.1%, with anemia, neutropenia, and sepsis as the most common complications requiring hospitalization. Initiatives such as rule OP-35 by the Centers for Medicare and Medicaid Service, improving access and providing coordinated care, early identification and management of symptoms, and expanding urgent care access could decrease these hospitalizations and the burden on healthcare. [Table: see text]