Pulmonary artery oxygen saturation (PA) was measured directly and estimated from venal cavae samples in 175 adults without intracardiac shunts to ascertain which of four formulas (MV1, MV2, MV3, or MV4) best estimated mixed venous oxygen saturation. Because the formula MV1, which favored IVC samples, most closely approximated pulmonary artery saturation, we recommend its use to estimate systemic flow in patients with left-to-right shunts. In addition, a difference between directly measured PA and calculated MV1 of 6% or greater indicates the presence of a left-to-right shunt in 97% of cases.