ABSTRACTBackgroundRevascularization decision‐making for saphenous vein grafts (SVGs) relies on angiographic lesion severity estimation, as studies on fractional flow reserve (FFR) for detecting ischemia in SVGs are scarce.AimsTo compare FFR and quantitative coronary angiography (QCA) of SVGs against myocardial perfusion imaging (MPI) and to establish an optimal FFR threshold for SVGs.MethodsThis cross‐sectional registry study included symptomatic patients with prior coronary artery bypass grafting who underwent single‐photon emission computed tomography, positron emission tomography, or stress perfusion cardiac magnetic resonance imaging and had FFR measurements of ≥ 1 SVGs. We matched the myocardial territory supplied by the SVGs to ischemia on MPI. The optimal FFR threshold for SVGs was determined using the Youden index. Diagnostic performance measures were calculated and compared for FFR (0.80 and the optimal threshold) and for QCA (diameter stenosis ≥ 50%).ResultsThis study included 80 patients (mean age 73 ± 7 years, 68 [85%] male) with 94 SVGs, of which 38 (40%) supplied ischemic myocardium. Areas under the curve between FFR and QCA were comparable (0.73 vs. 0.65, p = 0.181). The optimal cutoff value of FFR was 0.94. FFR ≤ 0.94 showed higher sensitivity (63%) and negative predictive value (75%) compared to FFR ≤ 0.80 (32% [p < 0.001] and 64% [p = 0.007]) and QCA (37% [p = 0.002] and 65% [p = 0.021]), but with lower specificity (75%) than FFR ≤ 0.80 (84%, p = 0.021). Positive predictive value and overall accuracy were similar across all methods.ConclusionsFFR and QCA had comparable moderate diagnostic performance for detecting SVG failure determined by MPI. The optimal FFR cutoff in SVGs is higher than 0.80, resulting in higher sensitivity and negative predictive value compared to FFR ≤ 0.80 and QCA, at the expense of reduced specificity.