Fractional flow reserve (FFR) is an important prognostic determinant in a clinical setting. However, its measurement currently requires the use of invasive pressure wire, while an angiographic technique based on first-pass distribution analysis and scaling laws can be used to measure FFR using only image data. Eight anesthetized swine were instrumented with flow probe on the proximal segment of the left anterior descending (LAD) coronary arteries. Volumetric blood flow from the flow probe (Qp), coronary pressure (Pa) and right atrium pressure (Pv) were continuously recorded. Flow probe-based FFR (FFRq) was measured from the ratio of flow with and without stenosis. To determine the angiography-based FFR (FFRa), the ratio of blood flow in the presence of a stenosis (QS) to theoretically normal blood flow (QN) was calculated. A region of interest in the LAD arterial bed was drawn to generate time-density curves using angiographic images. QS was measured using a time-density curve and the assumption that blood was momentarily replaced with contrast agent during the injection. QN was estimated from the total coronary arterial volume using scaling laws. Pressure-wire measurements of FFR (FFRp), which was calculated from the ratio of distal coronary pressure (Pd) divided by proximal pressure (Pa), were continuously obtained during the study. A total of 54 measurements of FFRa, FFRp, and FFRq were taken. FFRa showed a good correlation with FFRq (FFRa = 0.97 FFRq +0.06, r(2) = 0.80, p < 0.001), although FFRp overestimated the FFRq (FFRp = 0.657 FFRq + 0.313, r(2) = 0.710, p < 0.0001). Additionally, the Bland-Altman analysis showed a close agreement between FFRa and FFRq. This angiographic technique to measure FFR can potentially be used to evaluate both anatomical and physiological assessments of a coronary stenosis during routine diagnostic cardiac catheterization that requires no pressure wires.