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The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is an important measurement instrument for assessing the health-related quality of life (HRQOL) among heart failure patients. The purpose of this study was to translate and validate the MLHFQ in the Greek language. Three hundred forty-four consecutive adult patients from three General Hospitals, two in Athens and one in another part of the country, who were diagnosed with chronic heart failure, and 347 healthy controls were enrolled in the study from March 2009 to March 2010. The questionnaire instrument was translated from English, back-translated, and reviewed by a committee of experts. The psychometric measurements that were performed included reliability coefficients and Explanatory Factor Analysis (EFA), using a Varimax rotation and Principal Components Method. In a further step, confirmatory analysis (CFA)—known as structural equation modeling—of the principal components was conducted. The internal consistency of the Greek MLHFQ version was found to be 0.97, using Cronbach’s alpha coefficient. An exploratory factor analysis identified two domains that accounted for 72.5% of the variance of MLHFQ items; the area under the ROC curve was calculated at 0.942 and the logistic estimate for the threshold score of 24.50 provided the model with 95.1% sensitivity and 99.8% specificity. Additionally, the CFA demonstrated that the two-factor model offered a very good fit to our data. Our data indicate that the Greek MLHFQ is a reliable and valid tool for assessing HRQOL among patients with heart failure. Health …