OBJECTIVES: The FAME Study is an international multicenter randomized clinical trial (n=1,005), which proved a significant improvement in health outcomes for patients undergoing multivessel percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) measurement compared to PCI guided by angiography alone (ANGIO). The objective of this study is to estimate the impact of FFR-guided PCI on public health and on healthcare budget in France and Belgium and to compare these results with those of other European countries. METHODS: We used original patient-level data of the FAME Study (Tonino et al., NEJM 2009) to estimate health effects for France and Belgium. Utilities were measured with EQ-5D using French (time trade-off based) and Belgian Torrance transformed (visual analogue scale based) weights. Costs were based on French and Belgian prices and DRG catalogues. The size of the population eligible for the intervention was taken from national PCI registries to calculate number of major adverse cardiac events (MACE) avoided, quality-adjusted life years (QALYs) gained, and cost savings during a 2-year budget period (2011-2012) from the payer’s perspective. We estimated ranges based on best and worst case scenarios regarding benefits, costs and FFR uptake. RESULTS: For both countries, FFR led to more QALYs, less MACE and lower costs under different scenarios within 2-year time horizon. The public health impact of implementing FFR-guided PCI ranged from 6 to 44 QALYs gained in France and 12 to 234 in Belgium. MACEs avoided ranged from 284 to 2108 and from 23 to 467, respectively. Cost savings ranged from 4.8 to 28.9 and from 0.43 to 7.7 million EUR, respectively. CONCLUSIONS: Our impact study shows that FFR-guided PCI in patients with multivessel coronary disease is dominant and leads to considerably reduced numbers of MACE, more QALYs and substantial cost savings in the French and Belgian health care systems.