The aim of the study was to compare the quality of life (QL) of patients treated with single-agent paclitaxel versus doxorubicin as first-line chemotherapy for advanced breast cancer. 331 patients with advanced breast cancer were randomised, with 294 eligible for analysis. Patients completed both the EORTC QLQ-C30 questionnaire and the Rotterdam Symptom Checklist (RSCL) with six additional items, at baseline and after the third, fifth and seventh cycles of chemotherapy. A significant difference in progression-free survival in favour of doxorubicin caused a bias in the data with differences in expected completion rates of questionnaires beyond cycle three. Therefore, statistical comparisons were performed only for the first three cycles. Baseline compliance was 64% and 61% for the QLQ-C30 and RSCL questionnaires, respectively. Doxorubicin was associated with significantly more nausea/vomiting (P=0.001), loss of appetite (P=0.010) and a greater burden of disease and treatment (P=0.044), but with less bone pain (P=0.042) and rash (P=0.045) than paclitaxel. Both treatments were associated with improved emotional function and reduction in psychological distress at cycle 3. Longitudinal data suggested that doxorubicin was associated with less pain, specifically bone pain. Doxorubicin was more active but may have had more side-effects during the first three cycles. Long-term QL outcomes could not be assessed.