ABSTRACT: Based on randomized evidence, expert guidelines in 2011 endorsed shorter, hypofractionated whole breast irradiation (WBI) for selected patients with early-stage breast cancer and permitted hypofractionated WBI for other patients.To examine the uptake and costs of hypofractionated WBI among commercially insured patients in the United States.Retrospective, observational cohort study, using administrative claims data from 14 commercial health care plans covering 7.4% of US adult women in 2013, we classified patients with incident early-stage breast cancer treated with lumpectomy and WBI from 2008 and 2013 into 2 cohorts: (1) the hypofractionation-endorsed cohort (n?=?8924) included patients aged 50 years or older without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n?=?6719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement.Hypofractionated WBI (3-5 weeks of treatment) vs conventional WBI (5-7 weeks of treatment).Use of hypofractionated and conventional WBI, total and radiotherapy-related health care expenditures, and patient out-of-pocket expenses. Patient and clinical characteristics included year of treatment, age, comorbid disease, prior chemotherapy, axillary lymph node involvement, intensity-modulated radiotherapy, practice setting, and other contextual variables.Hypofractionated WBI increased from 10.6% (95% CI, 8.8%-12.5%) in 2008 to 34.5% (95% CI, 32.2%-36.8%) in 2013 in the hypofractionation-endorsed cohort and from 8.1% (95% CI, 6.0%-10.2%) in 2008 to 21.2% (95% CI, 18.9%-23.6%) in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures in the 1 year after diagnosis were $28,747 for hypofractionated and $31,641 for conventional WBI in the hypofractionation-endorsed cohort (difference, $2894; 95% CI, $1610-$4234; P?