Abstract Objectives This study aimed to investigate the cutoff of post–drug-eluting stent (DES) fractional flow reserve (FFR) for prediction of 1- to 3-year target vessel failure (TVF). Background FFR immediately after a DES implantation correlates with clinical events. However, the cutoff of post-DES FFR for predicting long-term clinical events remains understudied. Methods Between May 2012 and September 2013, a total of 1,476 patients who had FFR <0.8 at maximal and at baseline underwent DES implantation were prospectively studied in 9 centers. Post-DES FFR was repeat measured. The primary endpoint was the 1-year TVF rate after procedures. Receiver-operating characteristic curves were used to calculate the post-DES FFR value for TVF, then patients were classified on the basis of this value and followed up for 3 years. Results By the end of the first year, 88 (6.0%) TVFs were recorded. A post-DES FFR ≤0.88 strongly correlated with TVF. Disease in the left anterior descending coronary artery (LAD), stent length, and stent diameter were independent factors of impaired post-DES FFR, whereas post-procedure FFR ≤0.88 was the only predictor of TVF, with 40 (4.0%) TVFs in the FFR >0.88 and 48 (8.0%) in the FFR ≤0.88 group (p = 0.001), mainly driven by target vessel revascularization (3.8% vs. 8.8%; p = 0.005) and cardiac death (0.2% vs. 1.3%; p = 0.017). The difference in TVF between 2 groups was maintained through 3-year follow-up (p = 0.002). For patients with LAD lesions, a post-DES FFR ≤0.905 predicted 1-year TVF. Conclusions Post-DES FFR strongly correlated with TVF rate. Mechanisms attributed to and treatments for impaired FFR after stenting should be studied in future studies. (Post-DES FFR Predicts the Clinical Outcomes: DK CRUSH-VII, A Prospective, Multicenter, Registry Study DK CRUSH-VII; ChiCTR-PRCH-12001976 )