Abstract Background The fractional flow reserve (FFR) becomes a standard practice for revascularization decision-making in evaluating the functional significance of angiographically intermediate epicardial coronary stenosis. The quantitative flow ratio (QFR) is a novel method for rapid computational estimation of FFR without pressure wire and hyperemic induction. FFR has been reported to be associated with not only epicardial stenosis but also subtended myocardial mass (Vsub). In contrast, the relationship between QFR and Vsub has not been clarified. Purpose We sought to examine if subtended myocardial mass (Vsub) assessed by coronary computed tomography showed a significant relationship with QFR in comparison with FFR. Methods and results We performed a post-hoc analysis of 152 territories (LAD 116, RCA 25 and LCX 11 lesions) with angiographically intermediate-to-severe stenosis in 152 patients who underwent FFR assessment. The median FFR and QFR values were 0.76 (0.64–0.84) and 0.76 (0.72–0.83), respectively. The median diameter stenosis (%DS) and minimum lumen diameter (MLD) were 54.5 (43.9–64.2) and 1.2 (0.9–1.6), respectively. In total, 123 (80.9%) and 29 (19.1%) lesions showed concordant and discordant FFR and QFR functional classifications, respectively. The ability of Vsub/MLD2 to discriminate lesions with FFR≤0.80 and QFR≤0.80 was assessed compared with QCA data. FFR values were associated with Vsub (R=0.37, P<0.001). In contrast, a trend albeit no significant linear relationshipwas detected between QFR and Vsub (R=0.15, P=0.060). The area under the curve (AUC) of Vsub/MLD2 predicting FFR≤0.80 (0.88: 95% confidence interval [CI], 0.83–0.94)was significantly better than that of MLD (0.80: 95% [CI], 0.72–0.88) (P<0.001). On the other hand, the AUC of Vsub/MLD2 predicting QFR≤0.80 (0.82: 95% [CI], 0.75–0.90) was similar to that of MLD (0.80: 95% [CI], 0.72–0.87) (P=0.276). Multivariate analysis showed that the value of Vsub/MLD2 was an independent predictor of FFR≤0.80 (odds ratio [OR]: 1.09, 95% [CI]: 1.03–1.15, P=0.002), whereas it was not an independent predictor of QFR≤0.80. Conclusions Subtended cardiac mass volume derived from CT segmentation improved the diagnostic performance of angiography-derived parameters to identify ischemia-producing lesions when FFR used as a reference standard, whereas QFR showed non-significant relationship with subtended cardiac mass.