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The Minnesota Living With Heart Failure Questionnaire (MLHFQ) is the leading method for assessing quality of life in patients with heart failure (HF) around the world. However, unique, culture-specific variations in factorial structure have been identified. The current study examined the cross-cultural equivalence of an Italian version of the MLHFQ.Cross-sectional assessment as part of an HF study in Italy. Patients (n = 1,192; mean age = 72 years, SD = 11) completed demographics, the MLHFQ, and the Short-Form 12 (SF-12).A series of exploratory and confirmatory factor analyses were used to develop an appropriate factor model in the current sample.We initially fit a confirmatory factor analysis based on published psychometric work validating the MLHFQ. This did not provide adequate fit, and the sample was then randomly split into equivalent subsets to conduct factor analyses with cross-validation. In the first subsample, an exploratory factor analysis uncovered slight modifications to the proposed factor structure that resulted in much improved model fit. The final model included a higher order factor and three subscales: physical, emotional, and social. A cross-validation confirmatory factor analysis using this structure was conducted in the remaining subset to ensure broader applicability of the results. Correlations with the SF-12 were consistent with previous work using these measures.Some items of the MLHFQ are sensitive to differences across cultures, and factor structures vary based on where the scale is administered. In spite of these differences, the total score remains a valid and reliable indicator of quality of life in HF patients across cultures.Cultural influences on quality of life are important to consider when assessing patients' well-being in HF.