We report of a 78-year-old patient who underwent angioplasty for two de novo lesions in different aortocoronary venous bypass grafts. Whereas one lesion was treated by conventional stents, two adjacent lesions in a second bypass graft were covered by two newly designed stents with a polytetrafluorethylene (PTFE) membrane in between two layers of struts. The patient was first readmitted at month 5 with recurrent angina pectoris. High-grade in-stent restenosis of the lesion covered by the conventional stent was diagnosed, whereas the lesions treated by the membrane-covered stent revealed no restenosis. The patient underwent subsequent balloon angioplasty and was readmitted with unstable angina 8 months after the initial procedure. The angiogram revealed subtotal occlusion of the vein graft due to diffuse in-stent restenosis within the conventional stent. Undergoing re-PTCA, the patient received an additional membrane-covered stent placed over the proximal device. For the following 7 months, the patient stayed asymptomatic and underwent elective reangiography, which revealed a satisfying long-term result with no relevant luminal loss at the target site. This intraindividual comparison of stents in aortocoronary vein grafts suggests that PTFE membrane-covered stents might reduce restenosis as compared to conventional stents in venous bypass grafts. Furthermore, these stents potentially represent a new treatment strategy to fight in-stent restenosis in selected lesions.