Background: Evidence-based guidelines have endorsed use of hypofractionated whole breast irradiation (WBI), a shorter course regimen delivered over 3-4 weeks instead of conventional WBI over 5-6 weeks, for certain early stage breast cancer patients. In 2016, health insurer Anthem updated its clinical guidelines making hypofractionated WBI the standard for eligible members in its fully-insured plans. This change did not apply to self-insured groups allowing these members to serve as an internal control. The objective of the study was to evaluate the impact of this guideline change on adoption of hypofractionated WBI. Methods: We used Anthem claims data to identify women with incident breast cancer diagnosis followed by lumpectomy and subsequent WBI during 2015-2016. We further retained patients guideline-endorsed for hypofractionated WBI, i.e. those aged 50 or older, without prior chemotherapy or lymph node involvement. We defined hypofractionated WBI as 11-24 fractions (3-5 weeks of WBI) and conventional WBI as 25-40 (5-8 weeks of WBI). We compared pre-and post-intervention (year 2015 vs 2016) hypofractionated WBI rates between members in fully insured plans (intervention group) and members in other plans (comparison group) using a regression-adjusted difference-in-difference (DID) analysis controlling for age and comorbid conditions. Results: Compared to patients in comparison group (N = 2,333), those in intervention group (N = 728) were older (mean age 63.1 vs 61.4; p < .001) and had more comorbid conditions (mean Deyo-Charlson index 0.74 vs 0.60; p = 0.002). The rate of hypofractionated WBI increased from 53% in pre- to 68% post-intervention period for intervention group, an increase of 28%. In contrast, the rate changed from 58% to 63%, an increase of just 9%, in comparison group. The adjusted DID results suggested that change in guidelines increased the hypofractionated WBI adoption rate by 9% (p = 0.035). Conclusions: The changes in health plan guidelines resulted in higher rates of hypofractionated WBI adoption. Health plans could play an important role in accelerated adoption of evidence-based guidelines.