AbstractObjectivesWe sought to compare, in a national French registry (FrancePCI), the clinical impact of fractional flow reserve (FFR)‐guided percutaneous coronary intervention (PCI) compared with angio‐guided PCI at 1 year.BackgroundFFR has become the invasive gold standard to quantify myocardial ischemia generated by a coronary stenosis in patients with chronic coronary syndrome, but in clinical practice it is still underutilised to guide PCI compared to angiography (angio).MethodsWe extracted from the FrancePCI database all chronic coronary syndrome patients treated with PCI for coronary stenosis <90% between 2014 and 2019. Our composite clinical endpoint was the rate of major adverse clinical events (MACE).ResultsFourteen thousand three hundred eighty‐four patients with 1‐year clinical follow‐up were included. Among them, 13,125 had angio‐guided PCI (91%) and 1259 (9%) had FFR‐guided PCI. We observed a significantly higher rate of MACE in the angio‐guided group versus the FFR‐guided group: 1478 (11.3%) versus 100 (7.9%) (p < 0.0001), respectively, with hazard ratio (HR) of 1.440, 95% confidence interval (CI) [1.211−1.713] (p = 0.0004). This result was driven by the higher occurrence of death in the angio‐guided group versus the FFR‐guided‐group: 506 (3.9%) versus 17 (1.4%) (p < 0.0001), respectively, with HR of 2.845, 95% CI [2.099−3.856] (p < 0.0001). After adjustment for potential confounding factors, HRs were 1.287, 95% CI [1.028−1.613] (p = 0.028) for MACE and 2.527, 95% CI [1.452−4.399] (p = 0.001) for death. No significant differences between angio‐guided PCI and FFR‐guided PCI were observed for other clinical endpoints.ConclusionsFFR‐guided PCI improves outcome at 1 year compared to angio‐guided PCI with a reduction of 64% of death.