OBJECTIVES: The FAME Study is an international multicenter randomized clinical trial (n=1,005), which demonstrated a significant improvement in health outcomes for patients with multivessel coronary artery disease undergoing percutaneous coronary intervention (PCI) guided by fractional flow reserve measurement (FFR) compared to PCI guided by angiography alone. We performed a cost-effectiveness analysis along the FAME trial to estimate the cost effectiveness of FFR in France and Belgium and compared the 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 resource consumption, which was valued using prices from French and Belgian price lists and DRG catalogues (2010 values). Utilities were measured with EQ-5D based on French time trade-off and Torrance-transformed Belgian visual analogue scale (VAS) weights. We adopted a societal perspective and a one-year time horizon (i.e., follow-up of the FAME Study). Variability was examined using one-way sensitivity analysis and bootstrap resampling (n=5000). Results are expressed in incremental costs (EUR) and incremental QALYs. RESULTS: In both countries, FFR slightly improved QALYs (p>0.05) at significantly lower costs (p<0.05). Cost savings reached approximately 900 EUR/patient for both countries. For both countries, bootstrap analysis showed that FFR was cost saving in >50% of all bootstrap samples and cost effective in >90% when using a cost-effectiveness threshold of 50,000 EUR/QALY. The most influential cost components were prices for DES and FFR pressure wires. Cost-savings in France and Belgium are higher than recently presented results for Germany, the UK and Italy, where FFR is cost saving with savings ranging from 300-600 EUR/patient. CONCLUSIONS: In the context of the health care systems of Belgium and France, FFR-guided PCI is cost saving (dominant) in patients with multivessel coronary artery disease. These results are robust and in line with those of other European countries.