PURPOSE/OBJECTIVE The purpose of this study was to examine the impact of radiotherapy on quality of life (QOL) of breast cancer patients during and until 1 year post radiotherapy treatment. METHODS AND MATERIALS Thirty-nine breast cancer patients treated with breast conserving surgery were enrolled in a prospective study prior to whole breast radiotherapy (50 Gy plus a 10 Gy boost). No patient received chemotherapy. Data were collected before, at week 6 of radiotherapy, 6 weeks, and 1 year post-radiotherapy. The primary outcome variable was quality of life (QOL), measured by Medical Outcomes Study 36-Item Short Form Version 2 (SF-36) (SF-36). Risk factors potentially associated with total SF-36 scores and its physical and mental health component summary scores were also examined including age, race, marital status, smoking history, menopausal status, endocrine treatment, cancer stage, sleep abnormalities (assessed by the Pittsburgh Sleep Quality Index) and perceived stress levels (assessed by Perceived Stress Scale). Mixed effect modeling was utilized to observe QOL changes during and after radiotherapy. RESULTS Total SF-36 scores did not change significantly during and up to 1 year after radiotherapy compared to baseline measures. Nevertheless, increased BMI and increased perceived stress were predictive of reduced total SF-36 scores over time (p=0.0064, and p<0.0001, respectively). In addition, increased BMI was predictive of reduced physical component summary scores of the SF-36 (p=0.0011), while increased perceived stress was predictive of worse mental component summary scores (p<0.0001). Other proposed potential risk factors including skin toxicity from radiotherapy were not significant. CONCLUSIONS Radiotherapy did not worsen QOL in breast cancer patients. However, pre-radiotherapy patient characteristics including BMI and perceived stress may be used to identify women who may experience decreased physical and mental function during and up to 1 year post-radiotherapy.