This study examined the effect of artificial lung compliance (C) on pulmonary system (PS) impedance and right ventricular function during in-series attachment of the MC3 Biolung in adult sheep. Compliances, C, of 0–20 ml/mm Hg were tested at the Biolung inlet. Results indicate the PS 0th harmonic input impedance modulus was not affected by C. The PS first harmonic input impedance modulus (Z1) was 10.9 ± 3.2 mm Hg/(l/min) at C = 0 ml/mm Hg and minimized to 2.41 ± 0.79 mm Hg/(l/min) at C ≥ 0.5 ml/mm Hg. Cardiac output was 58% ± 10% of its pre-Biolung attachment, baseline value at C = 0 ml/mm Hg and was maximized to an average of 75% ± 11% at C ≥ 0.5 ml/mm Hg. The left ventricular lateral-to-anteroposterior axis length ratio, which decreases with leftward septal shift, increased with C from 0.52 ± 0.12 at C = 0 ml/mm Hg to 0.76 ± 0.06 at C = 5 ml/mm Hg (p < 0.05), but decreased slightly with C at C > 5 ml/mm Hg. Therefore, the ideal C for right ventricular function is at least 0.5 ml/mm Hg and may be as high as 5 ml/mm Hg to minimize septal shift.