Background. This study was designed to evaluate if patients in whom in-stent restenosis developed had an higher risk of early venous graft failure compared with normal patients. Methods. The study cohort comprised 120 patients ( 60 with previous in-stent restenosis and 60 controls) who received a total of 165 complementary venous grafts on the circumflex or right coronary artery system ( 84 in the restenosis group and 81 in the control group). All patients were prospectively followed-up and underwent reangiography at 5-years follow-up. Results. In the restenosis group, 28 venous grafts ( 33.%) were perfectly patent, 10 showed major irregularities, and 46 were occluded. In the control patients, 50 grafts ( 61.7%) were perfectly patent ( p < 0.001 compared with the restenosis series), 12 showed major irregularities ( p = .74), and 19 were occluded ( p < 0.0001). In contrast, the 5-year outcome of internal thoracic artery grafts was not affected by history of in-stent restenosis. Conclusions. Patients who developed in-stent restenosis have an higher risk of early venous graft failure compared with the control patients. Arterial grafts should probably be preferred in these patients.