Background: Weight gain concerns breast cancer patients, can impact quality of life, may lead to therapy non-adherence, and is associated with increased recurrence risk and mortality. Early placebo-controlled trials did not identify a clear correlation between Tamoxifen (TAM) and weight gain; gain due to aromatase inhibitors (AIs) is not well characterized. We hypothesized that weight gain occurs more frequently than previously reported in breast cancer patients receiving endocrine therapy. Methods: This is a retrospective chart review investigating body mass index (BMI) change in women after breast cancer therapy. Patients with early stage breast cancer and whom had BMI and treatment data (at least 90 days) from 2003-2012 were identified in The Columbus Breast Cancer Tissue Bank. Patients were separated by treatment received: chemotherapy with and without endocrine therapy vs. endocrine therapy alone (including both TAM and AIs) vs. no other treatment. Results: A total of 970 subjects were included in the analysis. At diagnosis and/or treatment initiation, patients’ mean BMI was 29.2 ± 7.0 kg/m²; mean age 53.7± 11.6 years; and average length of therapy/follow up per patient, 1833 days (range 90-3,990). Patients who received an AI alone had significantly decreased BMIs during therapy (-0.65± 0.29 kg/m², p = 0.025), whereas patients receiving chemotherapy alone, chemotherapy with TAM, or TAM followed by AI therapy, had significantly increased BMIs (0.51 ± 0.25, 0.73 ± 0.26, 1.01 ± 0.51 kg/m²; p = 0.039, 0.005, 0.045, respectively). Both older age and a higher BMI at diagnosis were associated with a significantly greater decline in BMI over treatment time (p < 0.001 and p < 0.001, respectively). In a multivariate regression model, after adjusting for age and initial BMI effect, the BMI change noted among different treatment groups was no longer significantly different (p = 0.43). BMI change was not statistically associated with treatment length (p = 0.26). Conclusions: Our review of a large, early stage breast cancer patient cohort showed no association between weight gain and endocrine therapy after adjusting for the effect of initial BMI and age at diagnosis. Additional study is needed to identify other factors impacting weight in this population.