We investigated the value of fractional flow reserve (FFR)-guided percutaneous coronary intervention (FFR-PCI) versus conventional PCI in patients with multivessel disease (MVD). Conventional PCI is performed by visual estimation of the stenosis. Deferral of PCI because of a FFR ≥0.75 is associated with low event rates. However, the value of FFR-PCI in patients with MVD is unknown. We prospectively enrolled 137 patients (312 vessels) with MVD to compare FFR-PCI and conventional PCI. In the FFR-PCI group, FFR of all vessels was performed, and PCI of stenoses with a FFR <0.75 was performed. In the conventional PCI group, patients underwent multivessel PCI by visual estimation of the stenoses. Procedural characteristics, event rates, and cost were compared between the 2 groups. In the FFR-PCI group, after FFR analysis in 57 patients (128 vessels), PCI was performed in 48 patients (53 vessels). In the conventional PCI group, 80 patients (184 vessels) underwent PCI. The average number of vessels per patient that underwent PCI and the cost of procedure were significantly greater in the conventional PCI group than in the FFR-PCI group (2.27 ± 0.50 vs 1.12 ± 0.30 vessels and $3,167 ± $1,194 vs $2,572 ± $934, respectively; p <0.001). The 30-month Kaplan-Meier event-free survival estimate was significantly higher in the FFR-PCI group than in the conventional PCI group (89% vs 59%, p <0.01). In conclusion, the results of the present study have demonstrated that in patients with MVD, compared with conventional PCI, FFR-PCI significantly reduces the number of vessels undergoing PCI, the event rate, and the cost of the procedure. © 2005 Elsevier Inc. All rights reserved.