Increasing evidence is available for the use of percutaneous coronary intervention (PCI) in selected patients with unprotected left main (LM) bifurcation coronary lesions. However, little data have been reported on recurrent in-stent restenosis (ISR) for LM bifurcation lesions. The aim of this study was to evaluate the efficacy of a drug-eluting balloon (DEB) for LM bifurcation ISR compared with that of a drug-eluting stent (DES).Between December 2011 and December 2015, 104 patients who underwent PCI for unprotected LM bifurcation ISR were enrolled. We separated the patients into 2 groups: (1) those underwent PCI with further DEB and (2) those underwent PCI with further DES. Clinical outcomes were analyzed.Patients' average age was 67.14 ± 7.65 years, and the percentage of male patients was 76.0%. A total of 75 patients were enrolled in the DEB group, and another 29 patients were enrolled in the DES group. Similar target lesion revascularization (TLR) rate and recurrent myocardial infarction (MI) rate were noted for both groups. A significantly higher cardiovascular mortality rate was found in the DES group (10.7% versus 0%, P = 0.020), and a higher all-cause mortality rate was noted in the DES group (21.4% versus 6.8%, P = 0.067).It is feasible to use DEB for LM bifurcation ISR. When comparing DEB with DES, similar TLR rates were found, but lower recurrent MI and lower cardiovascular death were noted for DEB treatment.