Background: Limited data are available on the economic burden of care for older patients with AML ineligible for intensive chemotherapy. This study aimed to evaluate healthcare resource utilization (HRU) and total cost of care (TCC) in this population. Methods: A retrospective observational study of Surveillance, Epidemiology, and End Results data (Jan 1, 2010 – Dec 31, 2015) linked to Medicare claims (up to Dec 31, 2017). Patients were ≥ 60 years old; newly diagnosed with AML; had ≥ 12 months of continuous Part A and B coverage before diagnosis; and initiated treatment on a hypomethylating agent: azacytidine (AZA) or decitabine (DEC) ≤ 90 days after diagnosis, or best supportive care (BSC). HRU (hospitalization, monitoring, transfusions, office visits, emergency department [ED] visits) and TCC reported in per patient per month (PPPM) were evaluated. Results: Among 3,905 patients identified, 877 (22%) received AZA, 899 (23%) received DEC, 2,129 (55%) received BSC. At a mean follow-up of 4.1 month (mo), mean TCC in BSC was $22,479.48 PPPM (standard deviation [SD]: $20,183.72). Hospitalization was the main cost driver (83.7% of TCC) in BSC, followed by Part B services and transfusions. At a mean follow-up of 11.9 vs. 13.0 mo, and mean treatment duration both at 5.4 mo, the mean TCC was $15,805.76 PPPM (SD: $19,368.16) in AZA vs. $20,518.71 PPPM (SD: $23,400.68) in DEC. All HRU decreased after AZA or DEC treatment initiation, except an increase in hospitalizations after treatment discontinuation (Table). During treatment on AZA and DEC, the main cost driver was hospitalization (60.7% vs. 60.9%) followed by drug costs and transfusions. After treatment discontinuation, hospitalization remained the main cost driver (77.2% vs. 78.9%) followed by transfusions and Part B services. Conclusions: This study quantifies the sizeable TCC in older patients with AML ineligible for intensive chemotherapy with hospitalization as the primary cost driver. Novel treatments that reduce hospitalizations, transfusions, and Part B services could lower the burden to the overall healthcare system.