Background: The CMS Oncology Care Model (OCM) was an episode payment model for patients with cancer receiving systemic therapy (chemotherapy, targeted therapy, immunotherapy, or hormonal therapy) that began in July 2016. Voluntarily participating practices received monthly care coordination payments of $160 per patient per month and were required to deliver enhanced services; they were eligible to share in savings if they achieved quality and spending targets (based on historic spending trended forward; all practices were in one-sided risk arrangements before 2019). Prior research identified savings of $499 per episode (excluding monthly payments) through OCM’s first 5 years, but no overall savings after including incentive payments. One concern about an episode payment model triggered by initiation of systemic therapy is that the financial incentives may prompt an increase in the total number of episodes. We assessed if OCM led to an increase in the likelihood of initiating systemic therapy. Methods: Using Medicare data, we studied care for beneficiaries enrolled in Parts A, B, and D of fee-for-service Medicare with index cancer diagnoses in 2010 through 2019. We assessed initiation of systemic therapy in the one year after the index diagnosis date. We studied two populations: (1) all patients with an index cancer diagnosis and no cancer diagnosis in the preceding two years, suggesting newly diagnosed or newly progressive cancers (incident cohort) and (2) patients with poor prognosis cancers. We used a difference-in-differences (DiD) analysis to assess systemic therapy initiation among patients with index cancer diagnoses who had office visits to medical oncology practices that were participating in OCM, compared with matched comparison practices (on number of patients attributed, number of physicians, number of medical oncologists, and academic affiliation, favoring matches within Hospital Referral Region), before and after OCM’s start in July 2016. Analyses adjusted for patient demographic and clinical variables. Results: Among 742,699 beneficiaries in the incident cancer cohort, 61.9% initiated systemic therapy within 1 year of their index diagnosis. Among 777,951 beneficiaries in the poor prognosis cohort, 58.2% initiated systemic therapy within 1 year of their index diagnosis date. OCM was not associated with the likelihood of initiating systemic therapy in the incident cohort (DID:-0.7 percentage point change, 95% CI:-1.9,0.4, P=0.19) or the poor prognosis cohort (DID:-1.0 percentage point change, 95% CI:-2.1,0.1, P=0.07). Conclusions: Despite financial incentives of episode payment models that may favor greater use of systemic therapy for patients with cancer, OCM did not increase the likelihood of initiating systemic therapy episodes among patients with newly diagnosed/newly progressive cancers or poor prognosis cancers who visited a medical oncology practice.