Graft reconditioning by dual hypothermic oxygenated perfusion (D-HOPE) is an emerging method to minimize ischemia-reperfusion injury (IRI), but it has never been applied in split liver transplantation (SLT). We describe the first case of ex situ SLT, with further left-lateral-segment hyper-reduction to monosegment-2 (S2)-graft, during D-HOPE in a liver from a 19-year-old brain-dead donor. The technique was adopted to minimize IRI because of donor’s hemodynamic instability and expected long ischemic times. During the procedure, D-HOPE had stable flows (portal: 200-300 mL/min; arterial: 50-80 mL/min) and pressures (portal: 6 mmHg; arterial: 25mmHg). The S2-graft was firstly disconnected from D-HOPE and transplanted into a 3.7 kg neonate with acute liver failure after 11 hours of total ischemic time, while the extended-right graft (ERG) continued to be double perfused. The ERG was transplanted in a 9-year-old boy with biliary atresia after 14 hours of total ischemic time. Both grafts showed early functional recovery and mild IRI at histology. After 14 months, the ERG recipient is well with normal liver function. S2-graft recipient developed portal vein thrombosis and underwent re-transplantation on postoperative day 14. In conclusion, this case proved that SLT is feasible under D-HOPE, without development of primary non-function and with mild IRI despite long ischemic times. Hence, further experience is needed to define the potential benefits of D-HOPE in SLT.This article is protected by copyright. All rights reserved.