Intracoronary-derived, pressure-based fractional flow reserve (FFR) is important for clinical decision-making in patients with 1-vessel coronary artery disease (CAD). In the present study, we investigated the prognostic value of FFR in patients with intermediate stenoses and multivessel CAD. Therefore, we analyzed 107 patients with stable angina pectoris who underwent myocardial perfusion scintigraphy and showed no perfusion defects in the region of the intermediate lesion. At angiography, FFR was determined distal to the intermediate lesion. FFR was abnormal (i.e., <0.75) in 15 of 107 stenoses (14%). Angioplasty of the intermediate stenosis was deferred based on the absence of a perfusion defect. Patients were followed for 1 year to document major cardiac events related to the intermediate lesion. At 1-year follow-up, a total of 12 (11%: no deaths, 3 myocardial infarctions, 2 coronary bypass operations, 7 coronary angioplasties) events occurred in the entire group that were related to the intermediate lesion. The event rate was significantly higher when angioplasty was deferred despite FFR <0.75 compared with the group with FFR > or = 0.75 (4 of 15 [27%] vs 8 of 92 [9%]; p <0.041). The relative risk of FFR for predicting cardiac events (mainly revascularization procedures) was 3.1 (95% confidence interval 1.1 to 8.9; p <0.05). In conclusion, deferral of angioplasty of intermediate coronary narrowings is safe based on FFR > or = 0.75 in this patient cohort; this coincides with previous reports in patients with 1-vessel CAD. Furthermore, these results suggest that FFR is more useful than single-photon emission computed tomography for clinical decision-making and risk stratification in patients with multivessel CAD.