Backgrounds: Angiographic evaluation overestimates the functional significance of jailed side branch (SB) lesions. We performed this study to assess the clinical outcomes of fractional flow reserve (FFR)-guided jailed SB intervention strategy. Methods: Patients with de novo bifurcation lesions with SB diameter >2mm and SB lesion length <10mm were consecutively enrolled. Patients with unstable clinical condition, ST-elevation myocardial infarction (MI) at target lesion territory, depressed LV function, chronic total occlusion and renal dysfunction were excluded. In FFR group (n=110), jailed SB FFR was measured after main branch stent implantation. SB intervention was performed if jailed SB FFR <0.75 and side branch stenting was permitted only in cases of < TIMI 3 flow. Conventional intervention group (n=110) was selected from SNUH database with the same patients' selection criteria. All lesions were treated with drug-eluting stents. Nine-month major adverse cardiac events (MACE: cardiac death, MI and target vessel revascularization (TVR)) and 2-year event free survival rate were evaluated. Results: There were no clinical and angiographic differences between 2 groups. In FFR group, SB FFR was not measured in 19/124 lesions due to slow flow of SB in 9, protocol violation in 6, adenosine induced AV block in 1, and SB re-cross failure in 3 lesions. SB intervention was performed in 24 lesions among 26 lesions with FFR<0.75. Conventional group had more SB intervention (44% vs. 30%, p=0.04) and had a tendency of more peri-procedural MI(14% vs. 8%, p=0.1) than FFR group. There was 1 case of follow up loss in FFR group and 2 in conventional group. Within 9 months, there was no difference in TVR rate between 2 groups (FFR-group: 4.7%, Conventional group: 3.7%). There was no death or MI. MACE after 9 months occurred in 4 patients (3 MI, 1 TLR) of conventional group. However, there was no difference in 2 year event free survival rate. Conclusion: FFR-guided SB intervention strategy resulted in less SB intervention with the same clinical outcomes as conventional intervention strategy.