Background: We evaluate the prognostic value of measuring fractional flow reserve (FFR) after percutaneous coronary intervention (post-PCI FFR) and intravascular imaging in patients undergoing PCI for three-vessel coronary artery disease (CAD) in the FAME 3 trial. Methods: The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with coronary artery bypass grafting (CABG) in patients with multivessel CAD. PCI was not non-inferior with respect to the primary endpoint of death, myocardial infarction (MI), stroke or repeat revascularization at 1 year. Post-PCI FFR data were acquired on a patient and vessel-related basis. Intravascular imaging guidance was tracked. The primary end point is a comparison of target vessel failure (TVF) defined as a composite of cardiac death, target vessel MI and target vessel revascularization at one year based on post-PCI FFR values. Cox regression with robust standard errors was used for analysis. Results: Of the 757 patients randomized to PCI, 461 (61%) had post-PCI FFR measurement and 11.1% had intravascular imaging performed. The median post-PCI FFR was 0.89 [IQR 0.85-0.94]. On a vessel-level, post-PCI FFR was found to be a significant predictor of TVF univariately (HR=0.67 [95% CI:0.48-0.93] for 0.1 unit increase, p=0.0165). On a patient-level, the single lowest post-PCI FFR value was also found to be a significant predictor of TVF univariately (HR=0.65 [95% CI:0.48-0.89] for 0.1 unit increase, p=0.0074). Post-PCI FFR was an independent predictor of TVF in multivariable analysis adjusted for key clinical parameters. Outcomes were similar between patients who had intravascular imaging guidance and those who did not. Conclusions: Post-PCI FFR measurement was a significant predictor of TVF on a vessel and patient level and an independent predictor of outcomes in a population with complex three-vessel CAD eligible for CABG. The limited use of intravascular imaging did not affect outcomes.