BACKGROUND: The aim of this study is to examine the associations between health utility (HU), health-related quality of life (HRQoL), and patient characteristics in postmenopausal osteoporotic (PMO) women. METHODS: Baseline data from a subsample of 1,245 participants of the Multiple Outcomes of Raloxifene Evaluation study, a randomized, placebo-controlled, multinational clinical trial to evaluate the safety and efficacy of raloxifene, were analyzed. The study cohort included 694 participants from non-European Union (non-EU) countries and 551 participants from EU countries. All participants with complete baseline HU and HRQoL assessments were included in the following analyses: 1) HU (HUI or EQ-5D) and HRQoL (QualEFFO or OPAQ and NHP) associations; 2) HU variability explained by HRQoL domains; and 3) the percentage of HU variability explained by statistically significant (p < 0.05) HRQoL domains, after adjusting for baseline characteristics. RESULTS: Several domains were significantly associated with HU scores. HU variance was well explained (41% to 61%) by 4 to 6 (p < 0.05) significant HRQoL domains. After controlling for baseline characteristics, 48% to 64% of the HU variance was well explained by 5 to 7 significant (p < 0.05) HRQoL domains. Additional trend analyses detected statistically significant decreases in HRQoL and HU scores with an increased number of vertebral and non-vertebral fractures. CONCLUSIONS: Both disease-targeted and generic HRQoL domains were well correlated with HU. A large percentage (48% to 64%) of the HU variance was explained by HRQoL, after adjusting for baseline characteristics. Both disease-targeted and generic HRQoL measures were significant predictors of HU. HRQoL and HU scores decreased with increased vertebral and non-vertebral fractures.