OBJECTIVES: The present study used long-term EQ-5D scores to evaluate patients with metastatic breast cancer (MBC) in a randomized control trial (RCT). METHODS: Patients with HER2-negative MBC were randomly allocated to the S-1 (an oral fluoropyrimidine) or taxane (paclitaxel or docetaxel) group. The primary endpoint was overall survival (OS), and QOL was a secondary endpoint. EQ-5D scores were surveyed at pre-treatment, three months after randomization, and every six months thereafter. Mean scores were assessed by repeated measured ANOVA including baseline, group, time and interaction of group and time. Minimal important difference (MID) analysis was also performed by defining the MID of EQ-5D as 0.05 or 0.1. When MID analysis was applied to the score during fist-line therapy, progression was treated as a competing risk. RESULTS: A total of 618 patients with MBC were randomly allocated to both groups (N=309 each). S-1 was non-inferior to taxanes for OS (median OS: S-1, 35.0 months; taxanes, 37.2 months). The number of patients in the EQ-5D population was 208 and 175 in S-1 and taxane groups, respectively. Mean duration of the EQ-5D response was 21 months for both groups. Mean EQ-5D scores up to 60 months were 0.748 and 0.741 in S1 and taxane groups, respectively. No significant difference was observed by ANOVA or MID analysis. During first-line therapy, mean EQ-5D score was 0.810 and 0.781 in S-1 and taxane groups up to 36 months, although in the post-progression period, scores decreased to 0.729 and 0.703, respectively. Gray’s test revealed that S-1 significantly delayed the decrease in QOL score. The size of the MID (0.05 or 0.1) did not influence the results. CONCLUSIONS: This study analyzed long-term EQ-5D scores of patients with MBC from RCT data. The QOL score of S-1 was higher during first-line therapy.