Background: Dose-adjusted (DA-) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a front-line treatment option for B-cell lymphomas such as double- or triple-hit diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphomas, primary mediastinal large B-cell lymphoma (PMBCL), and Burkitt lymphoma. DA-EPOCH is traditionally administered inpatient due to protocol complexity. However, many centers strive to transition to outpatient administration to decrease cost and improve the patient experience. The safety and cost savings of DA-EPOCH have not been fully elucidated outside of a safety-net health-system. Moffitt Cancer Center (MCC) developed an Inpatient/Outpatient (IPOP) program to facilitate administration of complicated inpatient regimens in the outpatient setting. We hypothesized that outpatient administration of DA-EPOCH in a tertiary comprehensive cancer center is both safe and cost-effective. Methods: We conducted a single-centered retrospective chart review including B-cell lymphoma patients who were 18 years or older and received DA-EPOCH at MCC from April 26, 2017 through August 10, 2019. Safety data included hospitalizations during outpatient administration and between cycles, culture-proven infections, and incidence of neutropenic fever, extravasations, drug spills, pump-malfunctions, and drug-related adverse events. Financial data was conducted through the institution’s financial department. Results: 88% (193 of 219) of DA-EPOCH cycles were administered outpatient to 56 patients. No patients were hospitalized during the outpatient administration of DA-EPOCH. As a result, 965 hospital days were saved. 23 patients (41%) were hospitalized between cycles for a total of 40 admissions, most commonly due to neutropenic fever (52%). No extravasations were documented throughout the study period. Drug spills and pump malfunctions occurred on a total of 3 and 4 cycles respectively. A total of 18 patients (32%) required vincristine dose adjustments due to neuropathy. Specific details regarding administration of DA-EPOCH in IPOP and supportive medications will be reported. IPOP DA-EPOCH administration was associated with an annual revenue increase of approximately $905,589 when compared to inpatient administration. Conclusions: DA-EPOCH can be safely administered in the outpatient setting. Outpatient administration was associated with a significant savings at a tertiary comprehensive cancer center.