Introduction: – The invasive quantification of coronary flow reserve (CFR), the index of microcirculatory resistance (IMR), and fractional flow reserve (FFR) allows to assess coronary physiology. Although semi-conductor (CZT) SPECT myocardial perfusion reserve (MPR) has been previously compared with FFR, there are no data documenting the relationships between CZT SPECT MPR on one hand and CFR and/or IMR on the other hand. We assessed the performances of noninvasive CZT SPECT MPR in comparison with invasively determined FFR, CFR, and IMR. Methods: – Rest and dipyridamole-induced stress myocardial blood flow and MPR were quantified using 99m Tc-SestaMIBI and a Discovery NM 530c camera in 26 patients with suspected or known coronary artery disease who underwent conventional invasive coronary angiography. Thermodilution-derived resting and adenosine-induced hyperemic mean transit times, distal intracoronary pressures, and mean aortic pressures were assessed for the quantification of FFR, CFR, and IMR values. Results: – Only 2/35 vessels presented with a pathological (<0.8) FFR. A moderate yet significant correlation was observed between regional CZT SPECT MPR and CFR (r=0.40, P =.02). The sensitivity, specificity, positive and negative predictive value, and accuracy of regional CZT SPECT MPR vs CFR were 69% [44-86%], 94% [74-100%], 91% [65-100%], 77% [56-90%], and 82% [65-93%], respectively. In territories without underlying CAD (n=32), CZT SPECT MPR values were significantly higher in those with CFR≥2 and IMR<25 (negative composite criterion, n=14) than in those with CFR<2 and IMR≥25 (positive composite criterion, n=8, CZT SPECT MPR, 2.6 [2.1-3.6] vs 1.6 [1.2-1.8]), P <.01). Regional CZT SPECT MPR displayed sensitivity, specificity, positive and negative predictive value, and accuracy of 87% [53-99%], 100% [78-100%], 100% [64-100%], 93% [70-99%], and 95% [77-99%] for the diagnosis of a positive composite criterion, respectively. Conclusions: – CZT SPECT MPR presented a moderate, significant correlation with thermodilution CFR and good diagnostic performances for the detection of patients at high risk of cardiovascular events (low CFR and high IMR) in the absence of obstructive CAD.