Value-based care is increasingly informing treatment decisions in radiation oncology. Although reimbursement differences have been examined for accelerated whole breast irradiation (AWBI) and conventional whole breast irradiation (CWBI), the cost of care delivery is poorly understood. This article describes our experience evaluating costs for altered fractionation in early-stage breast cancer using a time-driven activity-based costing (TDABC) model. Methods and Materials: Process maps were developed for 2 treatment regimens, AWBI (42.5 Gy in 16 fractions þ 10 Gy in 4 fractions boost) and CWBI (50 Gy in 25 fractions þ 10 Gy in 5 fractions boost). Cost was determined based on aggregate cost of personnel, materials, equipment, space, and utilities per unit time and based on the relative proportion of capacity used. The total reimbursement for each regimen was calculated as the aggregate of all billable events during a course of radiation therapy, based on the 2019 Centers for Medicare & Medicaid Services physician fee schedule database.