The New South Wales Breast Radiation Oncology Group has completed a prospective multicentre study of the impact of radiation therapy (RT) on acute toxicity and quality of life (QoL) in women with early breast cancer treated with breast conservation therapy. The patient group received adjuvant breast tangential RT after wide local excision of breast cancer. Acute toxicity and cosmesis was assessed quantitatively and qualitatively. European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) and Perceived Adjustment to Chronic Illness Scale (PACIS) were the QoL instruments used. Of 175 women, 34.3% described lethargy leading to a significant disruption to normal activity during RT. At week 6, this had reduced to 7.5% reporting significant lethargy. No negative effects on QoL were noted over the time period of RT; EORTC demonstrated no difference (P = 0.79). PACIS recorded a significant improvement in functioning (P < 0.001) from baseline to week 6. Univariate analysis on potential predictive patient, tumour and treatment factors demonstrated an association of baseline pre-RT breast discomfort with worse lethargy (P = 0.03), EORTC (P < 0.01) and PACIS (P < 0.01) measures. This study confirms the minimal impact of RT on patient functioning at 6 weeks post-treatment.