OBJECTIVES: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is one of the most used specific instruments for measuring quality of life in patients with heart failure. It comprises 21 items conforming a total score, as well as two domains: the physical and the emotional. The aim of this study was to evaluate the reliability, validity, and responsiveness of the Spanish MLHFQ. METHODS: Patients completed the MLHFQ and the SF-12 during their hospitalization for heart failure (n=1175), and 6 months after discharge (n=473). Reliability was assessed by Cronbach’s alpha coefficient. Confirmatory factor analysis (CFA) for categorical variables was used to study construct validity. Convergent validity was assessed by correlations between MLHFQ and SF-12 scales. To study known-groups validity, MLHFQ at 6 months were compared according to readmission. Responsiveness was evaluated by effect sizes and according to patients classified as improved, equal, or worsened than at baseline. RESULTS: Cronbach’s alpha was ≥0.80 for the three domains. CFA confirmed the two factor model, with factor loadings ranging from 0.56 to 0.87. Both Tucker-Lewis and Comparative Fit indexes were >0.90, but the root mean squared error of approximation was >0.08. The highest correlations were obtained between MLHFQ and SF-12 physical domains (r=–0.55), and between the emotional MLHFQ and mental SF-12 domain (r=–0.53), supporting the convergent validity. Known-groups validity was shown with significantly worse scores within patients with readmission (P<0.0001). Responsiveness parameters among improved patients were 1.20 and 1.05 for physical and total score, respectively, indicating large changes, and 0.59 for emotional domain, indicating moderate changes. CONCLUSIONS: The Spanish MLHFQ is valid, reliable and responsiveness 6 months after discharge for patients hospitalized with heart failure. Because its simplicity and ease of application, it may be useful in routine practice and clinical research. Further, its cross-cultural characteristics make it very useful for comparisons among countries.