ObjectivesTo compare drug-eluting balloons (DEBs) versus second-generation DES in the treatment of drug-eluting stent restenosis (DES-ISR). BackgroundThe optimal treatment of DES-ISR remains unclear. Several modes of treatment ranging from plain-old balloon angioplasty to repeated use of DES have yielded disappointing results. DEBs are increasingly been used in restenotic lesions; however, their use in DES-ISR is less established. MethodsWe evaluated all procedures between 2009 and 2011, involving DES-ISR that were treated either with DEB or second-generation DES. The measured end-points during the follow-up period were cardiac-death, target-vessel MI, TLR, TVR, and MACE defined as composite of cardiac-death, TV-MI, and TVR. ResultsTwo hundred and forty-seven patients (302 lesions) with DES-ISR were treated with either DEB (81 patients; 104 lesions) or second-generation DES (166 patients; 198 lesions). The mean age of patients was 66.19.4years. There were higher numbers of patients with diabetes in the DEB group (DEB 47% vs DES 33%; p=0.03). The mean length of DEB was significantly longer than the DES (35.4 vs 19.8mm; p<0.001). During the 12-month follow-up, there were no significant differences in the MACE rates (12.3% vs 8.4%; p=0.3) and TLR rates (9.9% vs 7.8%; p=0.6) between DEB and DES, respectively. On the multivariate analysis, use of DEB or DES was not the predictor of MACE (hazard ratio: 0.84, 95% CI: 0.46-1.85; p=0.6). There were no cases of definite or probable stent thrombosis in either group. ConclusionThere were no significant differences in the clinical outcomes between DEB and second-generation DES in the treatment of DES-ISR. These results should encourage operators to consider DEB in the treatment of DES-ISR, which offers certain advantages over DES. (c) 2015 Wiley Periodicals, Inc.