This is the case of a 77 year-old man with previous coronary by-pass grafting. After the occlusion of the saphenous vein graft to marginal branch, corrected by angioplasty and stenting with a bare metal stent (BMS), during the next 4 years he experienced multiple further episodes of in-stent restenosis of the first BMS. Angioplasty was performed each time. After 4 months since the last procedure, he had new episode of unstable angina. An EKG-gated, 64-row multislice CT (MSCT) examination was performed to evaluate the venous graft lumen, showing high-grade in-stent restenosis. Angiography confirmed the MSCT diagnosis, thus he underwent angioplasty and stenting with a drug eluting stent (DES). Thereafter, he remained stable for 4 years, when new anginal episodes led to a further coronary angiogram, showing progression of the atherosclerosic disease at the proximal and distal anastomosis of the venous graft; however, the previous implanted DES was patent. In the complex management of venous grafts restenosis, MSCT can be useful to help in detecting obstructive bypass graft disease. When revascularization is needed, DES have shown to be superior compared to BMS.