Background Identifying a functionally significant stenosis is difficult when several stenoses exist in one coronary artery. Fractional flow reserve (FFR) with pressure wire pull-back tracing can provide hemodynamic significance of individual stenosis. However, this strategy has not been evaluated well in a real world clinical practice. We performed this study to evaluate the physiologic and clinical outcomes of FFR-guided revascularization strategy in serial stenoses within one coronary artery. Methods Between Mar 2009 and Oct 2011, patients with multiple intermediate stenoses (40~70% in visual estimation) in the same coronary artery (vessel size >2mm in diameter) were prospectively enrolled. Serial stenoses were defined as 2 or more intermediate lesions with total length >40mm which were separated by clear non-diseased segment (>5mm). FFR was measured under maximal hyperemia induced by intravenous infusion of adenosine. Revascularization was deferred in vessels with FFR >0.8. If not, pressure wire pullback from distal to ostium of target vessel during sustained hyperemia was performed and the stenosis which caused largest pressure step-up was treated first. Revascularization of other stenoses was determined by FFR measured after first lesion stenting. Major adverse cardiac events (MACE) were defined as death, target vessel-related myocardial infarction and revascularization during the follow-up. Results A total of 104 coronary arteries and 215 lesions were included in this study. Mean distal FFR was 0.74짹0.11 in all vessels. FFR was measured in 167 times and there were no procedure-related complications. In 63 vessels (130 lesions) with FFR <0.8, baseline FFR was 0.67짹0.09 and increased to 0.85짹0.08 after stenting. In vessels with FFR <0.8, 75 stents (48 proximal, 27 distal) were implanted and the revascularization was deferred in 57.6% (75/130) of lesions. Two or more stents were implanted in only 12 vessels (19.0%). Proximal lesion stenting increased the FFR from 0.69짹0.08 to 0.84짹0.08 (21.7% increment) and distal lesion stenting, from 0.66짹0.10 to 0.87짹0.05 (31.8% increment). Pressure step-up of a non-treated lesion was increased from 7.5짹7.6 to 10.6짹6.5 mmHg (41.3% increment, p=0.016) after treating the first lesion. During mean follow-up of 1 year, target lesion revascularization was occurred in 1 stented segment. There was no MACE related to deferred lesions. Conclusion FFR-guided revascularization strategy in serial stenoses was safe and effective. This strategy can reduce unnecessary intervention in patients with multiple stenoses within one coronary artery.