OBJECTIVES: To evaluate and compare the performance of available disease-specific health-related quality of life (HRQL) instruments for use in heart failure. METHODS:  A systematic review identified 5 disease-specific HRQL questionnaires for use in heart failure (Minnesota Living with Heart Failure questionnaire [MLHFQ], Chronic Heart Failure questionnaire [CHFQ], Kansas City Cardiomyopathy questionnaire [KCCQ], Left Ventricular Disease Questionnaire [LVDQ], and the Quality of Life in Severe Heart Failure Questionnaire [QLSHFQ]). The 5 questionnaires were evaluated using EMPRO (Evaluating Measures of Patient Reported Outcomes), a tool for the standardized assessment of the psychometric properties and usability of patient reported outcome measures. Groups of four expert appraisers evaluated 8 attributes for each instrument and gave an overall recommendation after a consensus procedure. Scores ranged from 0 (worst possible score) to 100 (best possible score). Inter-rater agreement (intra-class correlation coefficient – ICC) was analyzed and median scores and ranges for all EMPRO attributes were calculated. An overall recommendation was provided (highly recommended, recommended with provisos, not recommended, unsure). RESULTS: Inter-rater agreement for EMPRO was generally acceptable (ICC of 0.48 - 0.93 for individual attributes). Median overall EMPRO ratings and attribute score ranges were: MLHFQ (59.8, 33.3–69.4), CHFQ (54.9, 38.1–72.2), KCCQ (47.2, 38.1–100), LVDQ (47.7, 11.1–76.7), and QLSHFQ (7.7, 5.6–26.6). The highest scores for all instruments except the QLSHFQ were on responsiveness (median scores from 5.6 to 100). Three of the questionnaires (MLHFQ, CHFQ, KCCQ) were recommended with provisos; the LVDQ and QLSHFQ were not recommended. CONCLUSIONS: Of the 5 instruments evaluated, 2 (MLHFQ, CHFQ) scored well on EMPRO and were recommended, whilst the others may be limited to use in particular types of study or require further investigation. This type of assessment can provide useful information for questionnaire selection. Funding: This work was supported by grants from Instituto de Salud Carlos III FEDER, (PI08/90724).