Objective: Nonadherence reduces the effectiveness of behavioral change regimens for promoting health and decreasing morbidities and mortality. Such is the case with endocrine therapies, which lower the likelihood of recurrence in the approximately 70% of women with hormone receptor-positive breast cancers. This investigation tests a model of contributors to objective adherence. Method: Women with breast cancer receiving their 1st endocrine therapy prescription (N = 130) were recruited from a large community oncology breast clinic. Participants completed three interview and questionnaire sessions at prescription initiation, one month and four months later. Questionnaires addressed patients’ experience with cancer and included measures of coping (COPE and Emotional Approach Coping), social support (Interpersonal Support Evaluation List), and depressive symptoms (Center for Epidemiologic Studies Depression Scale). At the initial appointment, participants were provided a Medication Event Monitoring System (MEMS) cap to assess adherence; the MEMS cap was collected at the 4-month follow-up appointment. Results: Structural equation modeling offered partial support for a mediational model, χ2(68, N = 130) = 77.47, p = .202, root-mean-square error of approximation = .03, comparative fit index = .97, standardized root-mean-square residual = .06. Greater social support at prescription initiation was associated with lower depressive symptoms 1 month later, which in turn were associated with higher objective adherence (MEMS) four months after study entry, controlling for significant covariates (p < .05). Use of avoidance-oriented coping was not statistically significantly related to depressive symptoms (p > .05). Conclusions: This model informs theory regarding medication adherence as well as intervention development for women prescribed adjuvant endocrine therapy.