Objective: Coronary artery disease is closely linked with inflammation, and the neutrophil-to-lymphocyte ratio (NLR) has emerged as a new inflammatory marker. Fractional flow reserve (FFR) is a well-established method for determining hemodynamic significance of coronary artery stenosis. In this study, we aimed to investigate the relationship between NLR and hemodynamic significance of coronary artery lesion as assessed by FFR. Methods: A total of 134 patients with FFR measurement between January 2012 and December 2013 were enrolled in this retrospective study. Patients with single intermediate-grade coronary artery stenosis were enrolled, and those with second intermediate or severe coronary artery stenosis were excluded from study. Patients’ NLR were calculated. An FFR value of ≤0.80 was accepted for hemodynamic significance. Statistical analysis was performed by the chi-square test, Student’s t-test, Mann–Whitney U test, logistic regression analysis, and ROC curve analysis. Results: Patients with hemodynamically significant lesions had higher NLR values (3.3±1.2 vs. 2.0±0.9, p<0.001). White blood cell count, male gender, high-density lipoprotein levels, platelet-to-lymphocyte ratio, and NLR were found to be possible confounding factors predicting hemodynamically significant coronary artery stenosis. In multiple logistic regression analysis, NLR remained as the only independent predictor for hemodynamically significant coronary artery stenosis. An NLR value of 2.4 had 87.5% sensitivity and 78.4% specificity for prediction of hemodynamically significant coronary artery stenosis. Conclusion: In present study, we showed that NLR was significantly higher in patients with hemodynamically significant coronary artery stenosis. We also found NLR to be an independent predictor of hemodynamically significant coronary artery stenosis as measured by FFR. Further studies are needed to find a causal relationship.