Current ex-vivo preservation systems (EVPS) are limited to patients over 40kg. This project aims to evaluate the ability of our novel ECMO-based system in maintaining the viability of low-weight donor porcine hearts over six hours. Our lab has developed an EVPS compatible with the Maquet Cardiohelp ECMO and other generally used perfusion pumps. The system was constructed via low-cost 3D printing. Initial feasibility study utilized donor hearts procured from juvenile pigs weighing less than 15 kg via sternotomy under cold arrest. The donor hearts were connected to the arterial outflow of the EVPS system via straight graft sewn to the innominate artery. The hearts were then placed in the novel venous return collection chamber that drains into the venous inflow, ensuring constant fluid submersion. All hearts were kept on EVPS for 6 hours. Aortic root pressure was continuously monitored directly, and blood gas sampling was conducted throughout the experiment with correction of electrolyte derangements. Tissue biopsies obtained from all four cardiac chambers at both the start and end of the EVPS run were sectioned and stained to compare against negative and positive control tissue. Tissue specimens were further processed for immunofluorescence against troponin T and 4′,6-diamidino-2-phenylindole. Epicardial ultrasound was conducted prior to procurement and post-6h for gross assessment of systolic function. Three hearts were maintained on ECMO-based EVPS for six hours, ensuring aortic pressure >90 mm Hg throughout the run. Lactate levels remained below 5 mmol/L and potassium between 4-5.5 mmol/L for all piglets. Biopsies from all heart chambers before and after perfusion revealed no signs of irreversible damage in contrast to pronounced pathological changes observed in positive controls as evidenced by wavy fibers, contraction band necrosis, and vacuolization. Markers of fibrosis and inflammation in the experimental groups were similar to those of the negative control. Echocardiography demonstrated grossly normal systolic function at start of operation and at the end of EVPS. Donor hearts procured from low-weight piglets and maintained on ECMO-based EVPS for up to six hours show no sign of irreversible damage. ECMO-based EVPS may facilitate long-distance procurement and transplantation of low-weight donor hearts which our current full transplant animal model is investigating.