Background: Coronary angiography is limited by its inability to assess the hemodynamic significance of a coronary artery stenosis. The assessment of the physiological significance of saphenous vein graft (SVG) lesions with a pressure wire to determine the fractional flow reserve (FFR) is lacking. Methods: FFR was determined in 10 SVG lesions of 10 males who had stress myocardial perfusion imaging (MPI) prior to referral for percutaneous coronary intervention for clinical indications. Results: All SVGs had a diameter stenosis (DS) >50% and 30% had a DS ≥=70%. A significant FFR was present in 30% of patients. Ischemia along the territory of the SVG was present in 20% of patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FFR <0.75 for the detection of ischemia on stress MPI were 50, 75, 33, 85, and 70%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FFR <0.75 for detecting ≥=70% DS on angiography were 33, 71, 33, 71, and 60%, respectively. There was no significant correlation between FFR and % DS (R2 5 0.1, P 5 0.35). Conclusion: The use of FFR to assess the physiological significance of SVG lesions is feasible and provides an acceptable specificity and negative predictive value compared to stress MPI. © 2008 Wiley-Liss, Inc.