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Summary: Background: The best way to treat in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The aim of this study was to evaluate angiographic restenosis and target lesion revascularization (TLR) at 8 months after intervention in patients with DES-ISR, and to identify predictive factors of subsequent TLR after treatment of DES-ISR. Methods and results: A total of 100 patients with 105 lesions underwent subsequent intervention for DES-ISR between April 2004 and January 2009. At baseline, focal and diffuse ISR were observed in 76.2% and 23.8%. DES-ISR was treated by five modalities: sirolimus-eluting stent (n =42); paclitaxel-eluting stent (n =24); balloon angioplasty (n =23); cutting balloon angioplasty (n =14); and bare-metal stent (n =2). Angiographic follow-up data were available for 95 lesions (91%). The rates of angiographic restenosis and TLR were 37.9% and 33.3%. Late loss of sirolimus-eluting stent, paclitaxel-eluting stent, cutting balloon, and balloon angioplasty were 0.50mm, 0.49mm, 0.93mm, and 1.10mm. By multivariate analysis, totally occluded ISR (OR 15.43, p =0.0005), diabetes mellitus (OR 3.45, p =0.02), and re-stenting with DES (OR 0.14, p =0.0002) were identified as independent predictors of TLR. Conclusions: The restenosis rate was significant in this cohort of patients with DES-ISR. Angiographic pattern of DES-ISR and diabetes mellitus are the most important predictors of TLR, whereas re-stenting with DES is protective. [Copyright &y& Elsevier]