The prostaglandin I-2 (PGI(2)) analogue iloprost, a potent vasodilator and inhibitor of platelet activation, has traditionally been utilized in pulmonary hypertension and off-label use for revascularization of chronic critical lower limb ischemia. This study was designed to assess the effect of 72 hr iloprost infusion on systemic ischemia poste-open elective abdominal aortic aneurysm (EAAA) surgery. Between January 2000 and 2007, 104 patients undergoing open EAAA were identified: 36 had juxtarenal, 15 had suprarenal, and 53 had infrarenal aneurysms, with a mean maximal diameter of 6.9 cm. The male-to-female ratio was 2.5:1, with a mean age of 71.9 years. No statistically significant difference was seen between the study groups with regard to age, sex, risk factors, American Society of Anesthesiologists (ASA) grade, or diameter of aneurysm repaired. All emergency, urgent, and endovascular procedures for aneurysms were excluded. Fifty-seven patients received iloprost infusion for 72 hr in the immediate postoperative period compared with 47 patients who did not. Patients were monitored for signs of pulmonary, renal, cardiac, systemic ischemia, and postoperative intensive care unit (ICU) morbidity. Statistically significantly increased ventilation rates (p = 0.0048), pulmonary complication rates (p = 0.0019), and myocardial ischemia (p = 0.0446) were noted in those patients not receiving iloprost. These patients also had significantly higher renal indices including estimate glomerular filtration rate changes (p = 0.041) and postoperative urea level rises (p = 0.0286). Peripheral limb trashing was noted in five patients (11.6%) in the non-iloprost group compared with no patients who received iloprost. Increased rates of transfusion requirements and bowel complications were noted in those who did not receive iloprost, with their ICU stay greater than twice that of iloprost patients. All-cause morbidity affected 67% of patients not receiving iloprost compared to 40% who did. Survival rates were significantly better with iloprost than without in both 30-day (p = 0.009) and 5-year cumulative (p = 0.0187) survival. Iloprost infusion for 72 hr after open AAA repair was associated with improved systemic perfusion and decreased systemic ischemia. Patients had a significant survival benefit at 30 days and 5 years and significantly improved renal, cardiac, and respiratory function.