Quantitative flow ratio (QFR) is a new opportunity to analyze functional stenosis during invasive coronary angiography. Together with a well-known intravascular ultrasound (IVUS) and a new player in the field, near-infrared spectroscopy (NIRS), it is gaining a lot of interest. The aim of the study was to compare QFR results with integrated IVUS-NIRS results acquired simultaneously in the same coronary lesion. We retrospectively enrolled 66 patients in whom 66 coronary lesions were assessed by NIRS-IVUS and QFR. Lesions were divided into two groups based on QFR results as QFR-positive group (QFR ≤ 0.8) or QFR-negative group (QFR > 0.8). Based on ROC curve analysis, the best cut-off values of minimal lumen area (MLA), minimal lumen diameter (MLD) and percent diameter stenosis for predicting QFR ≤ 80 were 2.4 (AUC 0.733, 95%CI 0.61, 0.834), 1.6 (AUC 0.768, 95%CI 0.634, 0.872) and 59.5 (AUC 0.918, 95%CI 0.824, 0.971), respectively. In QFR-positive lesions, the maxLCBI4mm was significantly higher than in QFR-negative lesions (450.12 ± 251.0 vs. 329.47 ± 191.14, p = 0.046). The major finding of the present study is that values of IVUS-MLA, IVUS-MLD and percent diameter stenosis show a good efficiency in predicting QFR ≤ 0.80. Moreover, QFR-positive lesions are characterized by higher maxLCBI4mm as compared to the QFR-negative group.