OBJECTIVE : Fatigue or tiredness is one of the most commonly reported symptoms in breast cancer patients treated with radiation therapy (RT). This study aimed to identify characteristics associated with fatigue in breast cancer patients receiving adjuvant RT. METHODS : Patients with non-metastatic breast cancer receiving RT at the Odette Cancer Centre from 2011 to 2017 were included in our study if they completed at least one ESAS pre- and post-RT. Information regarding patient, disease and treatment characteristics was retrieved from chart review. To identify variables associated with fatigue scores pre-RT, post-RT and changes in fatigue scores, a univariate and multivariate general linear regression analysis was conducted; p < 0.05 was considered statistically significant. RESULTS : Our study included 1223 female patients (mean age 59 years old) who completed ESAS on average 28 days before, and 142 days after RT. In multivariate analysis, higher baseline fatigue scores were found in women with higher disease stages (p = 0.001), and those who receive locoregional radiation (p < 0.001). No variables were significantly associated with post-RT fatigue scores. While adjuvant chemotherapy and locoregional RT were associated with higher baseline scores in univariate analysis, in multivariate analysis, they were associated with significant reduction in fatigue post-RT (p = 0.01, p = 0.007 respectively). CONCLUSIONS : Fatigue is associated with higher disease stage and receipt of locoregional radiation. While the relationship between anxiety or depressive symptoms and fatigue is well-established, a major gap exists in our understanding of its etiology and treatment; further investigation to address this can better improve patient quality of life.