© 2019 American Cancer Society Background: The authors examined Medicare spending and patient spending in older patients with chronic myelogenous leukemia (CML) over the first 5 years from the time of CML diagnosis in the tyrosine kinase inhibitor (TKI) era. Methods: Medicare beneficiaries with CML who were diagnosed between 2007 and 2012 at age >65 years were identified from the Surveillance, Epidemiology, and End Results (SEER)–Medicare database (805 beneficiaries). A noncancer Medicare beneficiary sample was frequency-matched based on age, sex, and race/ethnicity (805 individuals). Patients were followed until 5 years from diagnosis, disenrollment, death, or December 31, 2014, whichever came first. Total Medicare spending, service-specific spending, and amount owed by patients was estimated monthly and then summed over 60 months and averaged to generate annual spending. Results: The median age at the time of diagnosis of CML was 76 years (range, 66-102 years). Overall, 51.4% of patients received TKIs (27.8% received imatinib alone), 28% received non-TKI therapy, and 21% received no treatment. The 5-year survival rate for patients with ≥85% time receiving TKIs was 79% compared with 76% for noncancer controls versus 62% for those with <85% time receiving TKIs. Annual Medicare spending was found to be significantly higher for patients treated with TKIs ($143,053) compared with those treated without TKIs ($41,268 vs $10,498 for noncancer controls). Annual patient cost responsibility was $11,712 per patient receiving any TKIs versus $7330 for those receiving non-TKI outpatient chemotherapy versus $3561 for noncancer controls. Conclusions: Older patients with CML with adequate time receiving TKI therapy have 5-year survival rates that are comparable to those of their counterparts without cancer. However, TKI use is accompanied with significant Medicare and patient spending; patients receiving multiple TKIs (ie, dasatinib or nilotinib along with imatinib) constitute the group with the highest spending.