Background: Fractional flow reserve (FFR) is a physiologic parameter for specific epicardial coronary stenotic severity and it may be affected by the territory which the target lesion supplies. The purpose of present study was to evaluate the usefulness of FFR to determine PCI in small vessel (vessel diameter���2.75mm on coronary angiography) according to the lesions with myocardial blood supplying territory size in small vessels. Methods: We enrolled 457 patients, 544 de-novo lesions with intermediate to severe stenosis (>30% diameter stenosis (DS) by angiography) in small coronary vessels without myocardial infarction. FFR was measured after inducing hyperemia with adenosine. The lesions were divided into two groups. Group (A) of the lesions with large blood supply territory to myocardium was composed with the lesion located at the proximal to mid LAD, LCx, RCA and distal RCA (n=387 lesions). Group (B) of the small blood supply territory was composed with the lesion located at the side branch, PDA, distal LAD and LCx (n=157 lesions). Results: DS and minimal lumen diameter (MLD) had weak correlations with FFR (r=-0.378, p<0.001; r=0.373, p<0.001, respectively). FFR was higher in group B (0.83짹0.10 vs.0.79짹0.12, p<0.001) even though group B was more severe DS compared to group A (60.9짹13.9% vs. 55.9짹13.7%, p<0.001). The best cutoff value (BOV) of DS for prediction FFR<0.8 was 59.56% (AUC: 0.691, 95% CI: 0.650-0.729) in the total lesions. The BOV of DS for prediction FFR<0.8 in group A was 53.11% (AUC: 0.720, 95% CI: 0.672-0.764) whereas the BOV was 60.00% (AUC: 0.669, 95% CI: 0.590-0.742) in group B. Conclusions: This study demonstrated the small vessels less than 2.75mm can overestimate the stenosis severity by coronary angiography compared to physiologic stenosis assessed by FFR, especially when small vessel combined with small blood supply territory to myocardium.