Background Drug-eluting stents(DES) have been shown to dramatically reduce the rate of restenosis compared with bare metal stent. But the management of DES ISR is still a conflicting clinical problem and so far, little is known about the fate of DES ISR lesions. In the present study, we investigated the clinical courses and final outcomes of DES ISR lesions. Methods A total of 2,474 consecutive patients underwent successful implantation of sirolimus-eluting(SES, 1,705 patients, 2,092 lesions) or paclitaxel-eluting(PES, 882 patients, 1,211 lesions)stents. Of the 2,474 eligible patients(3,284 lesions), follow-up angiography at 6 months was obtained for 1,250 patients(50.5%, 1,694 lesions). Ninety patients(100 lesions) were treated for either SES or PES ISR(target lesion revascularization(TLR) rate by DES ISR:3.5%). The incidence of major adverse cardiovascular events(death, MI and TLR) was evaluated at 6 month(90 patients, 100 lesions) and 18 month(61 patients, 68 lesions) after stent implantation. Results Fifty two patients(57%) had diabetes. Of the 100 DES ISR lesions, 49% were SES and 51%, PES. The pattern of restenosis was focal in 80(80%), diffuse proliferative in 15(15%) and total occlusion in 5(5%). The incidence of diffuse pattern was more frequent in PES than in SES(37% vs 9%, p=0.002). Eighteen lesions(18%) were treated with balloon angioplasty, 56 lesions(56%), with cutting balloon, 21 lesions(21%), with new DES, 3 lesions(3%), with bare metal stent and 1 lesion with CABG(1%). Eleven lesions of 100 treated DES ISR needed repeated revascularization(re-TLR rate: 11%). One of repeated DES ISR TLR was finally resolved by CABG. Two patient(2%) had MI due to subacute stent thrombosis after ballooning of DES ISR. At 18 months follow-up after DES TLR, clinical results were available in 59 patients(97%) and there was 10 re-TLR and 1 MI but no cardiac death(18 month MACE rate:16.7%). In multivariate analysis(covariate: DM, SES, stent length and diameter), the predictor of repeated TLR of DES ISR was SES ISR(OR 5.29;95% CI, 1.08-25.64). Conclusion The pattern of DES ISR was mainly focal and the intermediate term follow-up results of TLR seem to be favorable.