Bleeding remains the most common complication of prolonged extracorporeal life support (ECLS). This study evaluated the Medtronic Minimax (Annaheim, CA) microporous oxygenator with the Carmeda Bio Active (heparin bonded) Surface (Stockholm, Sweden) for use in prolonged neonatal ECLS. Eight adult sheep were maintained on venovenous extracorporeal circulation (ECC) for a period of 4 days without systemic heparin. After 4 days of venovenous ECC without anticoagulation, there was no evidence of significant bleeding, circuit thrombosis, or systemic embolism. Gas exchange, hydrodynamic performance, coagulation, and biocompatibility studies suggest that the Minimax is safe and reliable for short-term or long-term ECLS in neonates.