Few data are available on the effectiveness of sirolimus-eluting stent implantation for the treatment of in-stent restenosis, and no data exist about the predictors of outcome after sirolimus-eluting stent implantation for complex in-stent restenosis (diffuse, proliferative, or total occlusion). From April 2002 to May 2004, 136 patients with 161 complex in-stent restenoses underwent sirolimus-eluting stent implantation. At 9 months, 5 patients had died (3 of cardiac and 2 of noncardiac causes), no reinfarctions had occurred, and 11 target vessel revascularization procedures had been performed. The target vessel revascularization rate was 8%, and the in-segment binary restenosis rate was 17%. The predictors of the risk of recurrence were unstable angina as the clinical presentation of in-stent restenosis, an ostial location of the target lesion, lesion length, and sirolimus-eluting stent diameter < or =2.5 mm.