Importance: Whether the improvement in myocardial perfusion provided by percutaneous coronary intervention (PCI) is associated with symptomatic relief or improved outcomes has not been well investigated. Objective: To investigate the prognostic value of the improvement in fractional flow reserve (FFR) after PCI (ΔFFR) on patients' symptoms and 2-year outcomes. Design, Setting, and Participants: This study is a post hoc analysis of data from patients undergoing FFR-guided PCI in the randomized clinical trials Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) 1 (NCT00267774; 2009) and FAME 2 (NCT01132495; 2012), with inclusion of 2 years of follow-up data. The FAME 1 trial included patients with multivessel coronary artery disease from 20 medical centers in Europe and the United States. The FAME 2 trial included patients with stable coronary artery disease involving up to 3 vessels from 28 sites in Europe and North America. Lesions from the group in the FAME 1 trial from whom FFR was measured and the group in the FAME 2 trial who received FFR-guided PCI plus medical therapy were analyzed. Data analysis occurred from May 2017 to May 2018. Interventions: Measure of post-PCI FFR. Main Outcomes and Measures: Vessel-oriented clinical events at 2 years, a composite of cardiac death, target vessel-associated myocardial infarction, and target vessel revascularization. Results: This analysis included 639 patients from whom pre-PCI and post-PCI FFR values were available. Of their 837 lesions, 277 were classified into the lowest tertile (ΔFFR≤0.18), 282 into the middle tertile (0.19≤ΔFFR≤0.31), and 278 into the highest tertile (ΔFFR>0.31). Vessel-oriented clinical events were significantly more frequent in the lowest tertile (n = 25 of 277 [9.1%]) compared with the highest tertile (n = 13 of 278 [4.7%]; hazard ratio, 2.01 [95% CI, 1.03-3.92]; P =.04). In addition, a significant association was observed between ΔFFR and symptomatic relief (odds ratio, 1.33 [95% CI, 1.02-1.74]; P =.02). Conclusions and Relevance: In this analysis of 2 randomized clinical trials, the larger the improvement in FFR, the larger the symptomatic relief and the lower the event rate. This suggests that measuring FFR before and after PCI provides clinically useful information.