Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for coronary artery disease has been validated. The present study aimed to identify the variables that influence FFR immediately after drug-eluting stents (DESs) implantation. We retrospectively analyzed 167 patients, who had been implanted with DESs at 6 Japanese institutions and had obtained the FFR values before and immediately after PCI. Intravascular ultrasound (IVUS) was used to build a PCI strategy and to decide the completion of the PCI procedure in all case. Patients were categorized into the following 2 groups according to FFR after PCI: the low FFR (≤0.80) group and the high FFR (>0.80) group. Despite successful PCI evaluated by coronary angiography and IVUS, 18.6 % of real-world patients were in the low FFR group. The proportion of the left anterior descending artery (LAD) was significantly greater in the low FFR group than in the high FFR group (87.1 vs 56.6 %; P < 0.01). Multivariate logistic regression analysis revealed that the LAD-to-non-LAD odds ratio for a low FFR (≤0.80) was 7.34 (95 % CI 1.63–32.95; P < 0.01) after adjustment for FFR value before PCI, suggesting that it is difficult to improve the hemodynamics of the LAD lesions even after successful PCI. The LAD was the strongest contributor to the inadequate recovery of FFR immediately after PCI, thus eliciting heed when treating the LAD lesions.