Endovascular treatment of femoropopliteal artery (FPA) disease with drug-coated balloons (DCBs) may face complications such as arterial recoil, dissection, and residual stenosis. Angiography has limited accuracy for evaluating blood flow through revascularized target lesions. Thus, there is a need for postprocedure hemodynamic assessment in treated limbs. This study aims to explore how postprocedure ankle-brachial index (ABI) influences outcomes following DCB treatment for FPA disease. This study included patients in a multicenter registry (K-VIS ELLA) treated with DCB for FPA disease between January 2006 and August 2021. Optimal postprocedure ABI cutoff for predicting clinically driven target lesion revascularization (TLR) was determined using receiver operating characteristic curve analysis. Independent predictors of TLR were identified using multivariable Cox regression analysis. A total of 654 limbs (514 patients) treated with DCB for FPA were evaluated by ABI at 1-day (median, interquartile range, 1 to 2 days) postprocedure and followed up for a median of 370 days. The optimal immediate postprocedure ABI cutoff value for predicting TLR was 0.72 (area under the curve, 0.68). Significantly improved TLR-free and major adverse limb event-free survival rates were observed with a postprocedure ABI ≥ 0.72 (hazard ratio [HR] = 0.24, 95% confidence intervals [CI] = 0.16 to 0.37, p < 0.001; HR = 0.25, 95% CI = 0.16 to 0.38, p < 0.001, respectively). Independent predictors of TLR were postprocedure ABI < 0.72 (HR 3.76; 95% CI, 2.33 to 6.07; p < 0.001) and presence of anemia (HR 2.01; 95% CI, 1.03 to 3.92; p = 0.041). An immediate postprocedure ABI is a significant predictor of TLR risk following DCB treatment for FPA disease, underscoring the value of hemodynamic assessment in optimizing angioplasty outcomes.