Background: The best wasy to treat in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The aim of this study was to evaluate the long-term outcomes after different modalities for treatment of DES ISR in a real world practice. Methods: Among 5490 patient treated with DES from May 2004 to January 2009, we analyzed consecutive 121 patients who were previously treated with DES who presented with angiographic ISR, and were treated with repeat (same or alternative) DES (reDES) (n=55) or conventional balloon angioplasty (POBA) (n=66). We evaluated the clinical outcomes in terms of major adverse cardiac event (MACE) (death, MI, and TLR). The mean clinical follow-up period was 24짹20.8 months. Results: The clinical and angiographic characteristics showed higher incidence of diabetes mellitus [40.9% (n=27) vs 21.8% (n=12), p=0.02], focal type (Mehran classification IA, IB, IC and ID) of ISR [54.6% (n=36) vs 36.4% (n=20), p=0.05] in POBA group, and bifurcation lesion [6.1% (n=4) vs 16.4% (n=9), p=0.04] in reDES group. There was no significant difference of MACE rate between the two groups [6.1% (n=4) for POBA vs 9.6% (n=5) for reDES, p=NS] including of no mortality, 0% vs 5.4% (n=3) in MI, and 6.11% (n=4) vs 9.6% (n=5) in TLR during follow-up period. Three stent thrombosis (acute=1, subacute=1, and late=1) were developed in the reDES group. Conclusion: In our registry, POBA seems to be as effective as other DES implantations for DES-ISR, if we perform POBA especially in focal type of ISR and simple lesion.