OBJECTIVES: Existing heart failure standard of care (SoC) provides symptom relief with no impact on changing the disease course.  This research assessed Payers’ perceived value and willingness to pay (WTP) for a novel oral therapy with significant improvement on top of SoC and a cell therapy providing potential disease modifying outcomes and enhanced mortality benefit. METHODS: An online survey with 22 US and EU-5 Payers assessing perceptions of current SoC therapies was conducted. A systematic evaluation of heart failure pharmaceutical, biologic and cell based therapies under clinical development was performed from which two hypothetical product profiles were developed: 1) a novel orally administered therapy; and 2) a recombinant cell based treatment via intramyocardial infusion.  Profiles were then tested by 30 in-depth interviews with US and EU-5 Payers.  RESULTS: Payer preference is based on the technology’s ability to meet efficacy targets treating the broadest heart failure patient segments. The oral agent was the preferred agent due to the clinical feasibility to develop with a WTP per day of US $8, UK £ 3 and EU €5 based on efficacy:  ≥ 28% RRR composite of CV death and HF hospitalizations; ≥ 25% RRR in CV mortality and ≥ 25% RRR in all-cause mortality.  The cell based therapy was cited as the most promising by improving symptoms and changing disease course with a WTP per treatment of US $6,500, UK £1,200 and EU €1,000 based on efficacy: improvement of NYHA functional class in ≥ 15% of patients in 1 year and ≥ 15% improvement in heart function. CONCLUSIONS: Payers see novel oral therapies as highly feasible and efficient in treating the broadest population and are willing to pay a premium. However, technologies that are disease modifying, reduce hospitalizations, and provide a significant mortality benefit are most desirable notwithstanding the considerable cost of treatment.