Percutaneous revascularization of saphenous vein grafts (SVGs) remains a challenging task. Drug-eluting stents (DESs) have been shown to decrease the incidence of restenosis in de novo native coronary artery lesions. However, their clinical value in SVGs remains to be established. We compared long-term clinical outcomes of percutaneous coronary intervention with DESs and bare metal stents (BMSs) for de novo lesions in SVGs. In a large prospective, multicenter registry, 360 patients underwent stenting of a de novo lesion in SVGs using BMSs (288 patients) or DESs (72 patients). Incidence of major adverse cardiac events (MACEs), including all-cause mortality, reinfarction, and target vessel revascularization, was recorded at a 12-month follow-up. Compared with the DES group, patients receiving BMSs were more likely to be men, to have chronic renal insufficiency or higher Charlson scores, but less likely to have undergone previous percutaneous coronary intervention. Incidence of MACEs at 12-month follow-up was similar in the 2 groups (17.8% in DES group vs 20.3% in BMS group, respectively, p = 0.460). Cox regression analysis identified age, chronic renal failure, cardiogenic shock at presentation, and ostial location of stenosis as independent predictors of long-term MACEs. In conclusion, our data suggest that rates of 12-month MACEs associated with the use of DESs and BMSs are similar in patients undergoing treatment of de novo lesions in SVGs.