PURPOSE: Value-based programs, such as the Oncology Care Model (OCM), seek to improve care for patients undergoing chemotherapy, while reducing total costs. The purpose of this study is to quantify the impact of adopting biosimilar granulocyte colony-stimulating factors (G-CSFs) for febrile neutropenia (FN) primary prophylaxis (PP) from a US practice perspective. METHODS: A 1-year economic analysis on real-world direct drug costs and health care resource utilization was conducted in a hypothetical cohort of 500 patients with nonmyeloid cancer receiving chemotherapy. The first model simulated total cost savings of biosimilar versus reference G-CSFs over six cycles of chemotherapy. The second model evaluated cost and outcome implications of expanding the use of biosimilar G-CSFs to an additional 10% of patients at intermediate FN risk. RESULTS: Based on real-world evidence over 1 year, a total of 121 of 500 patients received G-CSF prophylaxis resulting in cost savings that ranged from $0.54M US dollars (USD) (short-acting, eg, filgrastim) to $1.68M USD (long-acting, eg, pegfilgrastim) when switching from reference to biosimilar G-CSFs. Expanding the use of biosimilar G-CSFs allowed an additional 24 patients to receive prophylaxis of FN, leading to cost savings of $0.03M USD or $1.19M USD, with a reduction of $0.08M USD in FN-related resource utilization cost. The per-patient per-year cost saving for long-acting G-CSFs was about $3,000 USD. CONCLUSION: The implementation of biosimilar versus reference G-CSFs to OCM-participating practices results in a reduction of costs and facilitates achieving OCM metrics by improving patients' outcomes while expanding biosimilar G-CSFs access to patients at intermediate risk of chemotherapy-induced FN.