Background: Quality of life is increasingly used as an important end point in clinical trials of treatments for heart failure; thus, relationships between traditional clinical variables and quality of life need to be understood. Baseline data from an ongoing multi-institutional study of a surgically implanted cardiac support device (CorCap, Acorn Cardiovascular, Inc, St Paul, MN) positioned around the heart to halt progression of remodeling in patients with cardiomyopathy provide an opportunity to study the relationship between mitral regurgitation (MR) and quality of life in a group of relatively young patients. Objective: The objective of this study was to determine whether the degree of MR correlates with quality of life in patients presenting with significant symptoms of heart failure. Methods: Baseline MR was assessed by echocardiography and patients were stratified according to whether there was a clinical indication for mitral valve surgery. The effect of heart failure on quality of life was measured by the Minnesota Living with Heart Failure questionnaire (MLHF). The New York Heart Association class, exercise performance measured by peak oxygen consumption and the 6-minute walk test, and the SF-36 physical function measure were analyzed as potential mediating variables. Results: Mean MR grade was 2 ± 1.5 on a 0-to-4 (worst) scale (n = 260) and ejection fraction averaged 27% ± 9%. Most patients (82%) had New York Heart Association class III symptoms. Peak oxygen consumption averaged 14.7 ± 4.3 mL/kg per minute and average walking distance was 348 ± 83 m. Median (quartile range) SF-36 physical function was 35 (20-50) on a 0-to-100 (best) scale. Median MLHF score was 61 (47.5-77) on a 0-to-105 (worst) scale. The degree of MR and having an indication for mitral valve repair were not associated with the patients' quality of life. Controlling for symptoms and functional measures, older age was independently associated with better quality of life. Conclusions: The degree of MR was not related to MLHF scores, suggesting that surgery to reduce MR might not have predictable effects on quality of life. Further studies are needed to understand why younger patients reported worse quality of life and how this observation could impact therapy.