The present study examined the alternative treatment of sirolimus-eluting stent (SES) implantation for in-stent restenosis (ISR) of the unprotected left main coronary artery (LMCA). Twelve patients underwent SES deployment for bare-metal ISR in the LMCA. ISR were 24+/-11 mm in length and located at the ostial (n=1) and distal (n=11) portion of LMCA. Bifurcation lesions were treated with one of three techniques: the stent crossing the left circumflex artery (n=7), kissing stenting (n=2) or the Crush technique (n=2). All procedures were performed using intravascular ultrasound guidance. Periprocedural CK-MB elevation > or = 3 times normal occurred in 2 patients. There were no cases of significant narrowing in the left circumflex artery after the procedure. At the one-year follow-up, one patient died and there were no incidents of myocardial infarction or target lesion revascularization. The present study suggests that SES implantation may be a feasible therapeutic option for treating ISR in unprotected LMCA.