To explore the safety and efficacy of FFR-guided percutaneous coronary intervention (PCI) in vessels with severe diameter stenosis. Of 1090 patients undergoing fractional flow reserve (FFR) assessment from 2002 to 2009, we identified 167 patients in whom FFR was measured in at least one 70%-89% stenotic lesion. These patients were subdivided into an FFR-defer group (n = 49) if PCI was deferred (FFR > 0.80), and an FFR-perform group (n = 118) if PCI was performed (FFR ≤ 0.80). Comparatively, an additional 1176 patients undergoing PCI in at least one lesion with 70%-89% stenosis but without measurement of FFR served as a control (angiography-guided) group. Clinical outcomes were compared during a median follow-up of 49.0 months. The 5-year Kaplan-Meier estimated revascularization rates were 16% in the FFR-defer group and 33% in the FFR-perform group (P = 0.046). The incidence of major adverse cardiac events were comparable in these two groups (HR = 0.82, 95% CI: 0.37-1.82, P = 0.63). The number of stents placed was significantly lower in the FFR-guided group (0.9 ± 0.8 vs. 1.4 ± 0.8, P < 0.001). Functional revascularization for lesions with visually severe stenosis is clinically safe and associated with fewer stents use. This study suggests that extending the use of FFR to more severe coronary lesions may be reasonable.