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To examine the association between health-related quality of life (HRQoL) and mortality in patients with heart failure (HF). The potential association of HRQoL and mortality in patients with HF is unclear. We investigated this association in The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators (ICD) in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH). In DANISH, a total of 1116 patients with non-ischemic systolic HF on guideline-recommended therapy were randomized to ICD therapy or usual clinical care. HRQoL was assessed at randomization using the disease-specific Minnesota Living with Heart Failure Questionnaire (MLHFQ, 0–105, high score indicating worse HRQoL). Multivariable Cox proportional hazard models were used to compare hazard ratios (HR) for all-cause mortality according to MLHFQ above or below 45, as recommended by a recent meta-analysis, to identify patients with poor HRQoL. HRQoL was completed by 935 (84%) patients at baseline with a median follow-up of 67 months (IQR 47–83). Patients with poor HRQoL (MLHFQ score > 45, median 60 (IQR 53–71) , n = 350) had a higher incidence of all-cause mortality than patients with moderate/good HRQoL (MLHFQ ≤45, median 23 (IQR 13–33), n = 585), respectively 26% vs. 18% with an unadjusted HR of 1.57 (95% CI 1.19–2.08, p =.002), and an adjusted HR of 1.39 (95% CI 1.01–1.91, p =.04). Poor HRQoL was associated with an increased risk of all-cause mortality after adjustment for traditional risk factors. https: // clinicaltrials.gov/ct2/show/NCT00542945 (DANISH). • Poor quality of life is associated with mortality in patients with nonischemic heart failure • The association was obtained following adjustment for multiple traditional risk factors • Cardiovascular mortality was likewise associated to poor quality of life in crude models • Patients who experienced deteriorating quality of life within 8 months had a higher rate of mortality [ABSTRACT FROM AUTHOR]