The role of post-intervention minimal stent area (MSA) measured by intravascular ultrasound (IVUS) in target lesion revascularization (TLR) is unknown after stenting for in-stent restenosis (ISR). 223 ISR lesions treated with everolimus-eluting stents were analyzed retrospectively. Lesions were divided into 2 groups according to the postintervention MSA (=5.3mm2: 72 lesions, and >5.3mm2: 151 lesions). The cut-off point was determined based on receiver operating characteristic curve analysis. The cumulative 5-year incidence of TLR was significantly higher in the MSA =5.3mm2 group than in the MSA >5.3mm2 group (15.8% and 7.2%, P=0.01). After adjusting for confounders, the excess risk of the MSA =5.3mm2 group relative to the MSA >;5.3mm2 group for TLR remained significant (HR: 3.07, 95% CI 1.17-8.51, P=0.02). Using multivariate logistic regression analysis, we identified female sex (OR 2.39, 95%CI 1.06-5.49, P=0.04) and stent size =3.0mm (OR 13.43, 95%CI 6.23-32.38, P<0.0001) as the independent predictors of MSA =5.3mm2.