Backgrounds: FFR-guided percutaneous coronary intervention (PCI) strategy for side branch lesions after main branch intervention was reported to be safe. However, it might be difficult to use the same strategy for left main (LM) intervention. The aim of this study is to evaluate the safety and efficacy of FFR-guided PCI strategy in left circumflex artery (LCX) after left main to left anterior descending artery (LAD) crossover stenting. Methods: In this multi-center prospective pilot study, LM or ostial LAD disease were treated by PCI with drug-eluting stent (DES). After crossover stenting from LM to LAD, the ostium of LCX should have moderate to significant disease (diameter stenosis > 50%). PCI of jailed ostium of LCX was guided by FFR. If FFR was more than 0.80, the patients were deferred without any more procedure. If FFR was below 0.80, Kissing balloon technique or provisional stenting was performed. Major adverse cardiac events (MACE: cardiac death, myocardial infarction and target lesion revascularization (TLR)) were assessed at 9 months after the procedure. All analyses were performed on an intention-to-treat basis. Results: Twenty patients (mean age: 62 year-old, male: 65%) were enrolled. Mean percent diameter stenosis after crossover stenting and reference diameter of LCX ostium were 52짹18% and 2.91짹0.5mm, respectively. Sixteen patients (80%) were deferred. Three patients underwent additional procedure, guided by lower FFR (provisional stent deployment 1 patient, kissing ballooning: 2 patients). During the 9-month clinical follow-up, there was one patient (6.3%) who had MACE (TLR) in defer group. Another one patient was expired related noncardiac cause. There was no death, stent thrombosis or MI related to the lesions in which PCI was deferred according to FFR. Conclusions: In patients with LM distal or ostial LAD disease, FFR-guided PCI strategy in left circumflex artery (LCX) after left main to left anterior descending artery (LAD) crossover stenting resulted in excellent mid-term outcomes. FFR-guided strategy reduced the need for PCI.