To investigate the influence of operation sequence and staging on the outcome of aortic graft infection, we studied the mortality and amputation rates and incidence of new graft infection involving the extra-anatomic bypass (EAB) among 101 patients treated for secondary aortoenteric fistula (N = 43) or primary perigraft infection (N = 58). Patients were retrospectively grouped according to the operative treatment technique. Seven patients underwent infected graft removal (IGR) followed immediately by EAB (traditional). Fifty-seven patients were revascularized first, followed by immediate IGR in 38 patients (sequential) or by delayed IGR in 19 patients (staged). The median interoperative interval for the staged group was 5 days (range 2 to 31 days). Twenty patients underwent simultaneous IGR and in-line autogenous reconstruction (synchronous) and finally in 15 patients treatment consisted of IGR only with no extremity revascularization (none). The mean follow-up interval for all patients was 36.8 months. There was no statistically significant difference in mortality rate (traditional, 43%; sequential, 24%; and staged, 26%) or incidence of new graft infection (traditional, 43%; sequential, 18%; or staged, 16%) among those patients treated with EAB, although there was a trend toward an improved outcome with either sequential or staged treatment. There was a significantly lower amputation rate among sequential patients (11%) (p = 0.038) but not staged patients (16%) (p = 0.171) when compared with traditional treatment (43%). Staged operative treatment was associated with significantly less physiologic stress than sequential treatment as reflected by multiple perioperative metabolic variables (95% confidence limits). The treatment groups were comparable in the incidence of aortoenteric fistulas, culture-negative infections, emergent procedures, and appropriate antibiotic use. We conclude that reversed sequence or staged operative treatment of infected aortic grafts can be performed with no increased patient risk. Although traditional or sequential treatment may be required in the setting of acute hemorrhage, the staged operative approach is recommended for the treatment of chronic aortic graft infections.