The use of bare stents for the percutaneous intervention of saphenous vein bypass grafts (SVGs) is associated with a high subsequent rate of restenosis. To assess the impact of the sirolimus-eluting stent (SES), we studied 19 consecutive patients who underwent de novo SVG intervention treated solely with SES. Mean graft age was 10 years. Clinical presentation was an acute coronary syndrome in 68%. In total, twenty-two de novo lesions were treated with 35 SESs (mean=1.6 stents per lesion). Use of glycoprotein IIb/IIIa inhibitor therapy and distal embolization protection device were at operator discretion and were 42% and 32%, respectively. The rate of in-hospital major adverse cardiac events (MACE) was 11%, related to 2 patients with a creatine kinase rise consistent with peri-procedural acute myocardial infarction (AMI); a distal protection device was not utilized in either. Over a mean 12.5+/-2.6 month follow-up, one patient died from a non-cardiac cause, and there were no further AMIs. Target lesion revascularization was undertaken in 1 patient (5%); survival free of MACE was 84%. In conclusion, utilizing SESs for percutaneous intervention of degenerate SVGs is associated with a low rate of target vessel revascularization. Increased utilization of distal protection devices might reduce the peri-procedural rate of AMI.