A prospective, multicenter, open-label, randomized study was performed to assess the optimal treatment for in-stent restenosis (ISR) of drug-eluting stents (DESs). The results printed in the American Heart Journal revealed that there was no difference in terms of late loss at 9-month angiographic follow-up with treatment of DES ISR using drug-eluting balloon (DEB) or second-generation DES. However, DES demonstrated better angiographic results regarding minimal luminal diameter and percent diameter stenosis. Moreover, both treatment approaches were safe and effective up to 1 year after the procedure. The composite of death, myocardial infarction, or target lesion revascularization at 1 year was comparable between the two groups (DEB group versus DES group: 7% vs 4.7%).