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A longitudinal and comprehensive analysis of health-related quality of life (HRQOL) was performed during hospitalization for heart failure (HF) or soon after discharge.A post-hoc analysis was performed of the ASCEND-HF trial. The EuroQOL five dimensions questionnaire (EQ-5D) was administered to study participants at baseline, 24 h, discharge/day 10, and day 30. EQ-5D includes functional dimensions mapped to corresponding utility scores (i.e. 0 = death and 1 = perfect health), and a visual analogue scale (VAS) ranging from 0 (i.e. ‘worst imaginable health state’) to 100 (i.e. ‘best imaginable health state’). The association between baseline and discharge EQ-5D measurements and subsequent clinical outcomes including death and rehospitalization were assessed using multivariable logistic regression and Cox proportional hazards regression. A total of 6943 patients (97%) had complete EQ-5D data at baseline. Mapped utility and VAS scores (mean ± SD) increased over time, respectively, from 0.56 ± 0.23 and 45 ± 22 at baseline to 0.67 ± 0.26 and 58 ± 22 at 24 h and to 0.79 ± 0.20 and 68 ± 22 at discharge, and remained stable at day 30. Lower mapped utility scores at baseline [odds ratio (OR) per 0.1 decrease in utility score 1.03, 95% confidence interval (CI) 1.00–1.06] and discharge (OR 1.10, 95% CI 1.05–1.15) and VAS scores at baseline (OR per 10 point decrease 1.05, 95% CI 1.01–1.09) were significantly associated with increased risk of 30-day all-cause death or HF rehospitalization.Patients hospitalized for HF had severely impaired health status at baseline and, although this improved substantially during admission, health status remained abnormal at discharge.