Background Quantitative flow ratio (QFR), a novel functional angiography technique, computes fractional flow reserve (FFR) without pressure wires or adenosine. We investigated interindividual variations in the adenosine-induced hemodynamics during FFR assessment and their influence on QFR diagnostic performance. Methods and Results Patients with coronary stenoses who underwent intracoronary pressure and flow assessment were analyzed. Adenosine-induced hemodynamics during FFR measurement were determined by the percentage change in mean aortic pressure (%ΔPa) and the resistive reserve ratio (RRR). The diagnostic performance of QFR was evaluated and compared in each tertile of %ΔPa and RRR using FFR as reference. A total of 294 vessels (245 patients) were analyzed. Mean FFR was 0.80±0.11. Individuals showed a wide variation in the adenosine response in terms of %ΔPa (ranging from -75% to 43%; median, -9% [interquartile range, -3% to -17%]) and the RRR (ranging from 0.45 to 20.15; median, 3.1 [interquartile range, 2.1-4.9]). No significant differences for diagnostic efficiency of QFR were found between tertiles of %ΔPa (area under the curve for the receiver-operating characteristic analysis, 0.950 in tertile 1, 0.929 in tertile 2, and 0.910 in tertile 3; P=0.270) or between tertiles of the RRR (area under the curve for the receiver-operating characteristic analysis, 0.909 in tertile 1, 0.923 in tertile 2, and 0.959 in tertile 3; P=0.167). The classification agreement between QFR and FFR was not significantly modified by %ΔPa (tertile 1, 89%; tertile 2, 87%; and tertile 3, 86%; P=0.827) or by the RRR (tertile 1, 86%; tertile 2, 85%; and tertile 3, 91%; P=0.398). Conclusions Patients undergoing FFR assessment show large interindividual variations in the magnitude of adenosine-induced hemodynamics. However, such variations do not affect the diagnostic performance of QFR in assessing the functional relevance of observed stenoses.