Coronary microvascular dysfunction has important prognostic implications. Several hemodynamic indexes, such as coronary flow reserve (CFR), microvascular resistance, and zero-flow pressure (Pzf), were used to establish the most reliable index to assess coronary microcirculation. Fifteen swine were instrumented with a flow probe, and a pressure wire was advanced into the distal left anterior descending artery. Adenosine was used to produce maximum hyperemia. Microspheres were used to create microvascular dysfunction. An occluder was used to produce stenosis. Blood flow from the probe (Q p), aortic pressure, distal coronary pressure, and right atrium pressure were recorded. Angiographic flow (Q a) was calculated using a time-density curve. Flow probe-based CFR and angiographic CFR were calculated using Q p and Q a, respectively. Flow probe-based (NMRqh) and angiographic normalized microvascular resistance (NMRah) were determined using Q p and Q a, respectively, during hyperemia. Pzf was calculated using Q p and distal coronary pressure. Two series of receiver operating characteristic curves were generated: normal epicardial artery model (N model) and stenosis model (S model). The areas under the receiver operating characteristic curves for flow probe-based CFR, angiographic CFR, NMRqh, NMRah, and Pzf were 0. 855, 0.836, 0.976, 0.956, and 0.855 in N model and 0.737, 0.700, 0.935, 0.889, and 0.698 in S model. Both NMRqh and NMRah were significantly more reliable than CFR and Pzf in detecting the microvascular deterioration. Compared with CFR and Pzf, NMR provided a more accurate assessment of microcirculation. This improved accuracy was more prevalent when stenosis existed. Moreover, NMRah is potentially a less invasive method for assessing coronary microcirculation.angiography; blood flow; cardiovascular imaging; coronary microvascular function CORONARY ANGIOGRAPHY, a routine examination for patients with heart disease, provides an assessment of stenosis severity by visualizing the opacified arterial lumen. However, in many cases (12,40), the severity of myocardium ischemia correlates poorly with epicardial stenosis. Therefore, intracoronary physiological techniques have been developed to provide physiological evaluations for patients who undergo coronary angiography (8,34). Recently, the medical community's interest in coronary microcirculation has grown with the increasing awareness that microvascular dysfunction occurs in a number of myocardial disease states and has important prognostic implications (19,20). With this recognition comes the need for a method to accurately assess the functional capacity of coronary microcirculation for diagnostic purposes and to monitor the effects of therapeutic interventions targeted at reversing the extent of coronary microvascular dysfunction. To assess changes in the microcirculatory bed, several indexes have been proposed, such as coronary flow reserve (CFR), microvascular resistance (MR), and zero-flow pressure (P zf ). In the early 1990s, Gould et al. (14) introduced CFR...