Background: There is no enough data about the efficacy of repeat percutaneous coronary intervention (PCI) conducted in in-stent restenosis (ISR) lesions after drug eluting stent (DES) implantation. This study aimed to evaluate the clinical and angiographic out comes of repeat PCI in ISR lesions following DES implantation. Methods: This multi-center study enrolled 67 lesions of 62 patients who had ISR after DES implantation between April 2003 and march 2006. The ISR pattern was divided as follow; Group I: focal edge ISR (n=17), Group II: focal body ISR (n=36), Group III: non-focal ISR (n=14). Therapeutic strategy for ISR lesion including DES implantation and conventional treatment (CTx) such as, cutting balloon angioplasty and adjunctive balloon angioplasty was selected by operator���s decision. Major adverse cardiac events (MACE) such as, death, recurrent ischemia, target lesion revascularization angiographic restenosis rate were compared among groups. Results: 42 (79.2%) focal ISR were developed in SES and 11 (20.8%) focal ISR were in PES (p=0.95). Of 13 Non-focal lesions, 6 (46.1%) were total occlusive lesions. We conducted additional DES implantation in 20 ISR lesions as follow: 9 at group I (53%), 6 at group II (17%) and 5 at group III (36%) (p=0.050). Of these, 12 (60%) were treated with different DES and 8 (40%) were treated with the same DES. The other 47 lesions were treated by CTx. At 11 months clinical follow up , MACE was developed in 16.7% of Group II , 42.8% of Group III and there was no MACE in Group I (p=0.022). Angiographic restenosis was much higher in Group III (34%) compared to Group I (0%) and Group II (25%) (p=0.035). Conclusion: Repeat PCI in ISR lesion after DES showed much poor angiographic and clinical outcomes than de novo lesions. Focal ISR lesion, especially at the edge, showed better outcomes than diffuse type.