The NEAT trial reported considerable benefit for ECMF (epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil) of 28% for relapse-free survival (RFS) and 30% for overall survival (OS), when compared with classical CMF in early breast cancer. To assess tolerability, toxicity, dose intensity and quality of life (QoL) analyses were undertaken. All 2021 eligible patients had common toxicity criteria (CTC), delivered chemotherapy and supportive treatments details and long-term morbidities recorded. The QoL substudy used multiple validated measures. ECMF produced low CTC scores, although higher than CMF for nausea, vomiting, alopecia, constipation, stomatitis (P<0.001), infection (P=0.001) and fatigue (P=0.03). Supportive treatments required, however, were similar across randomised treatments. On-treatment deaths were more common with CMF (13) than ECMF(5). Optimal course-delivered dose intensity (CDDI > or =85%) was received more often by ECMF patients (83 vs 76%: P=0.0002), and was associated with better RFS (P=0.0006). QoL over 2 years was equivalent across treatments, despite minimally worse side effects for ECMF during treatment. ECMF benefit spanned all levels of toxicity, CDDI and QoL. There are no reported acute myeloid leukaemias or cardiac dysfunctions. ECMF is tolerable, deliverable, and significantly more effective than CMF, with no serious long-term toxicity or QoL detriment.