OBJECTIVES: The FDA is tasked with the evaluation of medical devices to determine the products’ safety and effectiveness. Utilization of patient-reported outcome (PRO) measures for medical device therapies poses special methodological challenges, due to small sample sizes and the often unblinded study design of device clinical trials. However, PRO's might prove useful in special circumstances to assist the Agency’s determination of device safety and effectiveness. One example is left ventricular assist device (LVAD) therapy for end-stage heart failure. METHODS: Clinical trials conducted in support of LVAD regulatory approval have demonstrated mortality benefits compared to optimal medical therapy alone. However, significant adverse events are also typically observed, including sepsis, bleeding and stroke. The regulatory challenge is to determine an acceptable tradeoff between mortality and adverse events. In this regard, PRO’s including quality of life measures could provide additional information to assist in decision-making for device approval and also guide development of a more informative product label. RESULTS: Three issues need to be addressed to boost the scientific validity of PRO’s in heart failure device trials: 1) the inherent unblinded study design for such devices makes PRO’s susceptible to patient bias, confounding study results; 2) differential rates of follow-up between treatment arms: patients too moribund to complete follow-up assessment tools might lead to underreporting of negative HRQOL data and confound study results; and 3) a consensus needs to be achieved regarding the selection of valid assessment tools for heart failure studies. CONCLUSIONS: PRO’s have promise in heart failure device evaluation, however, several important issues need to be addressed to properly incorporate such measures in studies intended for regulatory approval. The FDA welcomes dialogue with the clinical, academic and industry communities to develop appropriate PRO measures for heart failure device therapy.