Artificial lungs may serve as transplant alternatives to patients with respiratory failure. To provide a pulmonary replacement, the device cannot significantly alter right ventricular afterload. We sought to characterize cardiac load using a prototype artificial lung as a pulmonary replacement. An artificial lung was implanted into 13 adult sheep, 7 using a noncompliant original prototype and 6 using a modified device with a compliance chamber. Inflow was from the pulmonary artery and outflow into the left atrium. Pulmonary impedance was determined and pulse wave reflections analyzed. Resistance was similar in the original prototype artificial lung and in the native pulmonary circulation (3.0 vs 3.2 Woods units, p = 0.5). First harmonic impedance was significantly increased in the original prototype artificial lung (0.4 vs 5.9 Woods units, p < 0.01). High-amplitude pulse wave reflections were identified and right ventricular function was altered. The addition of compliance to the artificial lung reduced impedance at the first harmonic (5.9 vs 1.9 Woods units, p < 0.01), decreased the amplitude of pulse wave reflections, and normalized right ventricular function. A low-resistance but noncompliant artificial lung increases pulmonary impedance and alters right ventricular function. Addition of a compliance chamber reduces pulse wave reflections and normalizes ventricular function.