We compared the effects of two neonatal extracorporeal life support (ECLS) systems on circuit pressures and surplus hemodynamic energy levels in a simulated ECLS model. The clinical set-up included the Jostra HL-20 heart-lung machine, either the Medtronic ECMO (0800) or the MEDOS 800LT systems with company-provided circuit components, a 10 Fr arterial cannula, and a pseudo-patient. We tested the system in nonpulsatile and pulsatile flow modes at two flow rates using a 40/60 glycerin/water blood analog, for a total of 48 trials, with n = 6 for each set-up. The pressure drops over the Medtronic ECLS were significantly higher than those over the MEDOS system regardless of the flow rate or perfusion mode (144.8 +/- 0.2 mm Hg vs. 35.7 +/- 0.2 mm Hg, respectively, at 500 mL/min in nonpulsatile mode, P < 0.001). The preoxygenator mean arterial pressures were significantly increased and the precannula hemodynamic energy values were decreased with the Medtronic ECLS circuit. These results suggest that the MEDOS ECLS circuit better transmits hemodynamic energy to the patient, keeps mean circuit pressures lower, and has lower pressure drops than the Medtronic Circuit.