The optimal endpoint after balloon angioplasty remains poorly defined. This study aimed to characterize post-balloon angioplasty anatomical and physiological indexes by quantitative flow ratio (QFR) and to compare their prognostic impacts on long-term clinical outcomes. This retrospective study included 106 lesions from 106 patients who underwent percutaneous coronary interventions with drug-coated-balloon (n = 69) or plain-old-balloon-angioplasty (n = 37). Analyses measured minimum lumen diameter (MLD) and percent diameter stenosis (%DS) as anatomical indexes; QFR of target vessel (QFR-vessel) and QFR-gradient (ΔQFR between proximal and distal segments of the lesion) as physiological indexes. Primary endpoint was target lesion revascularization (TLR) after the index procedure. TLR occurred in 21 (20 %) lesions. TLR group showed significantly smaller QFR-vessel (0.79 ± 0.12 vs. 0.85 ± 0.12, p = 0.03), as well as greater QFR-gradient (0.12 ± 0.07 vs. 0.04 ± 0.03, p < 0.0001) at post-procedure compared with non-TLR group. The percentage of angiographically significant dissection was also more frequently observed in TLR group compared with non-TLR group (47.6 % vs. 14.1 %, p < 0.0001 for log-rank). In the multivariate analysis, angiographically significant dissection and QFR-gradient at post-procedure was significantly associated with TLR. In the receiver-operating characteristics curve analysis, the area under the curve for predicting post-procedural TLR was significantly greater for QFR-gradient than for MLD and residual %DS (p < 0.0001 for MLD and p = 0.0003 for residual %DS at post-procedure). The best cut-off value of post-procedural QFR-gradient for predicting TLR was 0.08. Post-procedural QFR-gradient across the lesion was a statistically independent and stronger predictor of TLR, compared with anatomical indexes. Display omitted •Post-procedural QFR after POBA or DCB was a predictor of subsequent TLR.•Per-lesion QFR analysis was a stronger predictor, compared with per-vessel analysis.•The best cut-off value of post QFR-gradient for predicting TLR was 0.08.•QFR analysis may help identify the optimal endpoint of balloon angioplasty.