The objective of this study was to compare the reproducibility and sensitivity of the instantaneous hyperemic flow versus pressure slope index (i-HFVP) and coronary flow reserve (CFR). The i-HFVP is the slope of the relationship between diastolic hyperemic coronary flow and diastolic aortic pressure, normalized for bed weight. In contrast to CFR (the ratio of hyperemic to basal coronary flow), the i-HFVP has been shown to be independent of changes in aortic pressure, heart rate, contractility, and preload. To compare reproducibility, i-HFVP and CFR were measured three times in eight dogs instrumented with high-fidelity micromanometers and flow probes, allowing for full hemodynamic recovery between phases (15 to 40 minutes). Maximum hyperemia was induced with intravenous adenosine. The sensitivity of i-HFVP and CFR was assessed in 16 instrumented dogs. Measurements were performed for one basal state and for five subcritical incremental stenoses created with a screw occluder during hyperemia. Intraclass variability correlation coefficients were 0.96 for i-HFVP but only 0.56 for CFR. Both i-HFVP and CFR showed significant decrements with each increasing stenosis. However, the percentage reductions at each level were significantly greater for the i-HFVP. The difference in percentage reduction favoring increased sensitivity of the i-HFVP ranged from 11% to 23%. It was concluded that the i-HFVP is more reproducible and more sensitive to the presence of stenoses than CFR.