OBJECTIVES: The Appalachia region experiences excess cancer mortality and a lack of access to cancer care resources. There is limited research examining adjuvant treatment use disparities in this region. This study aims to explore adjuvant endocrine therapy (AET) utilization in Appalachia, and delineate the effects of access to cancer on AET use.  METHODS: We linked female breast cancer patients identified in cancer registries from the Appalachian counties in four states (KY, NC, OH, PA) to 2006-2008 Medicare claims data. We included patients with invasive, non-metastatic, hormone-receptor-positive breast cancer and assessed the prevalence of receiving guideline-recommended AET. We then assessed AET adherence among those who received guideline-recommended AET using the Medication Possession Ratio (MPR), and determined non-persistence, defined as exceeding a 60-day medication gap.  We also used survival analyses to examine the influences of adherence and persistence on overall survival.  RESULTS: Only 450 of the 946 eligible patients (47.6%) received guideline-recommended AET, which was significantly associated with shorter travel time to receive care, dual Medicare and Medicaid eligibility, being unmarried (vs. married), and living in Pennsylvania (vs. Ohio). The non-adherence rate was about 31% and non-persistence rate was 30% over an average follow-up period of 421 days. Tamoxifen, relative to aromatases, was associated with higher odds of adherence (OR = 2.82, p < 0.001) and a lower risk of non-persistence (HR = 0.40, p < 0.001). Side effects like pain may be an important factor leading to non-adherence and early discontinuation. Non-adherence to and non-persistence with AET were associated with higher risks of all-cause mortality. CONCLUSIONS: In Appalachia, geographic and socioeconomic factors such as travel time to receive care and healthcare plan type are important elements that could contribute to disparities in access to adjuvant treatment, while treatment choice and medication-related factors may exert strong influences on AET use behaviors.