Sirolimus-eluting stent (SES) is established to be effective in reducing restenosis. Repeat revascularization, however, is still required in up to 5-8% of patients. In this study, we analyzed clinical and angiographic variables that might be related with SES re-restenosis and variables related with re-restenosis after repeat SES implantation for SES restenosis. We also assessed clinical outcomes at 2-year follow-up after percutaneous coronary intervention (PCI) for SES restenosis. Repeat revascularization for SES restenosis was performed in 113 patients with 140 lesions. Of the 140 lesions, follow-up coronary angiography (CAG) was performed on 117 lesions (101 patients) and revealed 46 SES re-restenotic and 71 non-re-restenotic lesions. In multivariate analysis, SES-in-SES-strategy and reference diameter before the second PCI were independent predictors of re-restenosis after PCI for SES restenosis. However, the reference diameter was the only independent predictor of re-restenosis after SES-in-SES. Major adverse cardiac events (MACE) at 2 years were found in 44 patients (43.5%), and target lesion revascularization (TLR) was performed in 33.7% of patients after SES restenosis. In conclusion, the incidence of MACE and TLR was relatively high in patients with SES restenosis, but the placement of another SES on larger-diameter vessels may be an effective strategy for the second PCI.