PURPOSE The Oncology Care Model (OCM) is an episode-based alternative payment model for cancer care that seeks to reduce Medicare spending while maintaining care quality. We evaluated the impact of OCM on appropriate use of supportive care medications during cancer treatment. METHODS We evaluated chemotherapy episodes assigned to OCM (n = 201) and comparison practices (n = 534) using Medicare claims (2013-2019). We assessed denosumab use for beneficiaries with bone metastases from breast, lung, or prostate cancer; prophylactic WBC growth factor use for beneficiaries receiving chemotherapy for breast, lung, or colorectal cancer; and prophylactic use of neurokinin-1 (NK1) antagonists and long-acting serotonin antagonists for beneficiaries receiving chemotherapy for any cancer type. Analyses used a difference-in-difference approach. RESULTS After its launch in 2016, OCM led to a relative reduction in the use of denosumab for beneficiaries with bone metastases receiving bone-modifying medications (eg, 5.0 percentage point relative reduction in breast cancer episodes [90% CI, –7.1 to –2.8]). There was no OCM impact on use of prophylactic WBC growth factors during chemotherapy with high or low risk for febrile neutropenia. Among beneficiaries receiving chemotherapy with intermediate febrile neutropenia risk, OCM led to a 7.6 percentage point reduction in the use of prophylactic WBC growth factors during breast cancer episodes (90% CI, –12.6 to –2.7); there was no OCM impact in lung or colorectal cancer episodes. Among beneficiaries receiving chemotherapy with high or moderate emetic risk, OCM led to reductions in the prophylactic use of NK1 antagonists and long-acting serotonin antagonists (eg, 6.0 percentage point reduction in the use of NK1 antagonists during high emetic risk chemotherapy [90% CI, –9.0 to –3.1]). CONCLUSION OCM led to the reduced use of some high-cost supportive care medications, suggesting more value-conscious care.