Background and Objectives : We compared long term outcomes according to method of the target lesion revascularization (TLR) in treatment of the in-stent restenosis (ISR) of the drug eluting-stents (DES). Subjects(Materials) and Methods : Of total 3160 patients with the DES in Asan Medical Center, 138 who had the TLR with the DES or balloon angioplasty were selected. (98 with the DES, 40 with simple or cutting balloon angioplasty). We compared the incidence of stent thrombosis, death and especially the repeated TLR during 4-year follow-up period. Results : Baseline characteristics were similar for each group. There was no significant difference in the stent thrombosis-free survival rate (89.5% vs. 89.8%, DES vs. balloon, p=0.95), death (1% vs. 0%, DES vs. balloon, p=0.53) and the repeated TLR-free survival rate (80.5% vs. 88.0%, DES vs. balloon, p=0.38). In multivariable adjusted Cox regression analysis, there was also no significant difference between the two groups in the repeated TLR rate (hazard ratio, 1.56; 95% confidence interval, 0.66 to 5.81, p=0.21) These results were sustained after subgroup analysis according to the focal or diffuse ISR type. Conclusion : In the treatment of the ISR of the DES, balloon angioplasty had similar outcomes with the DES in the repeated TLR rate. Further large trial is needed to delineate the role of the DES and balloon angioplasty for the DES failure.