Retrograde oxygen persufflation as a supplement of cold storage during the preservation period has the potential to better utilize ischemically damaged marginal livers in the experimental setting. Retrograde oxygen persufflation was applied in selected livers to demonstrate feasibility in the clinical setting and to investigate potential beneficial effects. Between 4/04 and 3/05 5 marginal otherwise discarded livers with warm ischemic damages from deceased donors (age 52 [37-64]) were accepted for transplantation. All organs were distantly procured and shipped to our center. Immediately after arrival, filtered humidified gaseous oxygen was given via the hepatic veins for at least 60 minutes with a pressure up to 18 mm mercury. Liver biopsies were analyzed for ATP content before and after persufflation. All patients (age 55 [46-66]) survived without retransplantation, had good initial function and are alive and well after minimum follow-up of two years. Bleeding from pinpricks stopped spontaneously after 5-10 minutes after reperfusion but was prolonged in one patient with severe coagulopathy until correction. One patient developed arterial thrombosis at postop day 0. He fully recovered after thrombectomy. Another patient developed subcapsular hematoma, which was removed at postop day 10. On routine postoperative biopsies vascular structures appeared undamaged. ATP levels in pre-reperfusion biopsies revealed a more than twofold increase of ATP content compared to biopsies before persufflation. Retrograde oxygen persufflation preservation is feasible and save in the clinical setting, improves early aerobic metabolism and therefore potentially improves primary organ function after liver transplantation.