BACKGROUND: We sought to examine the relationship between health-related quality of life (HRQL) and a first emergency rehospitalization and mortality in patients with heart failure (HF) having a wide variation in ventricular ejection fraction and functional status. METHODS: Prospective study conducted with 394 patients admitted for HF-related emergencies at 4 Spanish hospitals. Baseline HRQL was measured with a generic questionnaire, the Medical Outcomes Study 36-item Short Form Survey (SF-36), and with an HF-specific instrument, the Minnesota Living With Heart Failure (MLWHF) questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) for hospitalization and death on the basis of HRQL scores. RESULTS: During a median follow-up of approximately 6 months, 138 patients (35.0%) underwent a first emergency rehospitalization and 70 (17.8%) died. After adjustment for biomedical, psychosocial, and health care variables, the frequency of hospital readmission was higher in patients with worse scores on the SF-36 physical functioning (HR, 1.65; 95% confidence interval [CI], 1.11-2.44; P = .01), general health (HR, 1.73; 95% CI, 1.19-2.52; P = .003), and mental health (HR, 1.65; 95% CI, 1.10-2.47; P = .02) subscales. Results were similar for the mortality end point. For the MLWHF questionnaire, worse overall and worse physical and emotional summary scores were associated with higher mortality. CONCLUSIONS: Worse HRQL is associated with hospital readmission and death in patients with HF. The magnitude of this association, for both physical and mental HRQL components, is comparable to that for other well-known predictors of hospital readmission and death, such as personal history of diabetes, previous hospitalizations, and treatment with angiotensin-converting enzyme inhibitors.