Background: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-containing regimens are frequently utilized in lymphoma, however, outpatient EPOCH or modified inpatient/outpatient EPOCH has not been described extensively. We transitioned inpatient EPOCH to the outpatient setting and modified EPCOH to be given in the inpatient setting with rituximab outpatient to improve quality of care and access to patient assistance programs. We describe our institutional experiences with inpatient and modified EPOCH to the outpatient setting. Methods: A single-center, institutional review board-approved retrospective study was conducted for adults receiving EPOCH-based regimens. Clinical and financial data were collected by chart review for each patient. Descriptive statistics were utilized for analysis. Results: A total of 31 patients received 116 cycles of an EPOCH-containing regimen (11 [9.5%] inpatient), 54 [46.5%] outpatient, and 51 [44.0%] hybrid inpatient and outpatient). Nine outpatient cycles, 9 (17.6%) hybrid cycles and no inpatient cycles resulted in admissions for FN. Two inpatient cycles were delayed (18.2%) due to disease-related procedures and one (9.1%) was delayed due to low blood counts. Five (9.2%) outpatient cycles were delayed due to logistics (i.e. insurance delays, scheduling errors) and two (3.7%) outpatient cycles were delayed due to disease-related adverse events (bowel obstruction, chest pain). Transitioning EPOCH to the outpatient setting decreased overall costs for hospital stays on average by $19,792 per cycle with an overall approximate cost savings to the health-system of 1,114,992 dollars with 432 bed days saved. Costs savings to patients with medications assistance programs is pending final analysis. Conclusions: EPOCH-containing regimens can be safely transitioned into the outpatient setting, side effects can be monitored and outcomes optimized, to better adapt treatment strategies for individualized patient therapies. As new healthcare payment models are developed, outpatient treatments allow for adaptive financial options both for the health-system and the patient.