Technology advances in cancer care have paralleled rapidly increasing expenditures in radiation therapy. The use and costs of shorter cancer radiation therapy offer potential utility in clinical practice. We evaluate use and expenditures of Medicare Advantage (MA) beneficiaries receiving hypofractionated whole breast irradiation (HF-WBI) compared with conventionally fractionated whole breast irradiation (CF-WBI) in the United States and examine the relationship of patient characteristics with HF-WBI use. We performed a retrospective analysis of radiation therapy in MA beneficiaries using private employer-sponsored insurance claims for a pooled cross-sectional evaluation from 2009 to 2017. The study population included female MA beneficiaries with early-stage breast cancer treated with lumpectomy and whole breast irradiation. A total of 9957 women received HF-WBI, and 18,920 received CF-WBI. Older age, greater distance from home to treatment facility, and a higher proportion of college graduates in the community of residence were associated with increased HF-WBI use. Mean insurer-paid radiation therapy expenditures were significantly lower for HF-WBI versus CF-WBI (adjusted difference, $4113; 95% CI, $4030-$4,197). Mean patient out-of-pocket expenditure for HF-WBI was $426 less than that of CF-WBI. Across US states, geographic variation existed in the ratio of costs for HF-WBI relative to CF-WBI (range, 0.41-0.87). HF-WBI use among MA beneficiaries with breast cancer has dramatically increased over time, surpassing CF-HBI as the dominant form of radiation therapy. HF-WBI clinical adoption has outpaced any continual cost decrease, despite wide variation across US states for this shorter radiation therapy treatment. As MA enrollment continues to expand, identifying the drivers of HF-WBI use and the sources of variation in costs of HF-WBI will help direct the quality of cancer care delivered to Medicare beneficiaries.