OBJECTIVES: Advanced Therapy Medicinal Products (ATMPs) are therapies expected to cure, halt or slow down the progression of many disabling diseases among which Heart Failure disease (HF). About 1000 ATMPs are in development of which 65 already in phase III. Stem cell therapies targeting HF are in development. Our objective is to evaluate ATMPs Drug budget impact (DBI) on Health Insurance (HI) in HF assuming various efficacy profiles. METHODS: A Markov model was developed to compare two strategies: Standard of care (SoC) and ATMPs for a representative cohort of HF patients over a 10-year period, with 1-month cycle-length. Model input data, SoC costs and quality-adjusted life-year (QALY) data were derived from published sources. We assumed that one procedure allows achieving the outcome. Five efficacy scenarios were tested to evaluate the cost of ATMP procedures assuming an ICER threshold of 50,000€/QALY. DBI was computed by multiplying the procedure cost by HF prevalence in France. RESULTS: In the first and second scenarios, 100% and 50% patients were cured respectively with a DBI of 348,144,688,850€ and 192,523,977,243€. In the third and fourth scenarios, probabilities of progression were reduced by 50% or 33% leading to respective DBI of 1,186,221,568€ and 1,606,499,643€. In the fifth scenario, patients did not progress further and the DBI was 2,355,086,110€. CONCLUSIONS: If ATMPs successfully reach the market, they will bring unprecedented clinical and social benefits to patients and society. However they are likely to severely impact the French health service budget thus threatening sustainability of the healthcare system. Without deep policy changes in the pharmaceutical interventions pricing, the sustainability of health system in the EU Member States will be severely threatened.