To investigate whether the health-related quality of life (HRQOL) of patients switching from tamoxifen to anastrozole in a randomized trial is identical to that of those who continued tamoxifen after 1-4 years of adjuvant tamoxifen in Japanese postmenopausal breast cancer patients. Eligible patients for the randomized trial, the National Surgical Adjuvant Study of Breast Cancer 03, were recurrence-free postmenopausal women who had received definitive surgery for primary breast cancer with positive hormone receptor(s), and had been taking tamoxifen for 1-4 years postoperatively. They were randomly assigned to continue tamoxifen or to switch to anastrozole for a total duration of five years. Subjects were asked to reply to a self-administered QOL questionnaire survey to assess HRQOL (FACT-B [breast cancer scale], FACT-ES [endocrine symptom scale]) and psychological distress (CES-D: Center for Epidemiologic Studies Depression scale) at randomization (baseline), 3 months, 1, and 2 years after randomization, respectively. At baseline 694 patients (346 in the tamoxifen group and 348 in the anastrozole group) responded to the survey. The total scores of FACT-G, FACT-ES, and those of the FACT-G physical well-being subscale were statistically significantly better in the tamoxifen group than in the anastrozole group (P = 0.042, 0.038, and 0.005, respectively). However, there was no statistically significant difference between the treatment groups in the CES-D scores. Continuation of tamoxifen treatment after adjuvant tamoxifen for 1-4 years may provide Japanese breast cancer patients with better HRQOL than by switching to anastrozole.