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Abstract: Background: Limited comparative studies assessing the health-related quality of life (HRQL) in heart failure (HF) patients with preserved vs. low ejection fraction (LVEF) have been disparate. Aims: The aims of this study were a) to characterize HRQL in a large population of HF patients with preserved and low LVEF and b) to determine the factors associated with worse HRQL. Methods: Patients with symptomatic HF (NYHA Class II–IV) enrolled in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) HRQL study completed the Minnesota Living with Heart Failure questionnaire at randomization. Patients were stratified into 2 HF cohorts: preserved LVEF (>40%) and low LVEF (≤40%). Results: In 2709 of the eligible 2744 (98.6%) patients, the summary scores ranged from 0 to 105 (mean 40.9). There were no differences in overall responses of HF patients with preserved vs. low LVEF (41.1 vs. 40.8). Independent factors associated with worse HRQL in both populations included female gender, younger age, higher body mass index, lower systolic blood pressure, greater symptom burden, and worse functional status. Conclusions: In symptomatic HF patients, HRQL is equally impaired in both preserved and low LVEF populations. Targeting improvement in symptoms and HRQL is an important treatment objective in all HF patients. [Copyright &y& Elsevier]