Use of femoral-femoral veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) for cardiopulmonary support during lung transplantation can be inadequate for efficient distribution of oxygenated blood into the coronary circulation. We hypothesized that creating a left-to-right shunt flow using veno-arterio-venous (VAV) ECMO would alleviate the differential hypoxia. Total 10 patients undergoing lung transplantation were enrolled in this study. An additional inflow cannula was inserted into the right internal jugular (RIJ) vein for VAV ECMO. During left one-lung ventilation using a 1.0 inspired oxygen fraction (FiO2), the left-to-right shunt flow was incrementally increased from 0 to 500, 1,000, and 1,500 ml/min. The arterial oxygen partial pressure (PaO2) and oxygen saturation (SaO2) were measured at the proximal ascending aorta and right radial artery. The ascending aorta gas analysis revealed that six patients had a PaO2/FiO2 ratio less than 200 mm Hg at a 0 ml/min shunt flow. The PaO2 (SaO2) values were 48.5 ± 14.8 mm Hg (80.9 ± 11.6%) at the ascending aorta and 77.8 ± 69.7 mm Hg (83.3 ± 13.2%) at the right radial artery. As the left-to-right shunt flow rate increased over 1,000 ml/min, the PaO2 and SaO2 values for the ascending aorta and right radial artery significantly increased. In conclusion, femoral-femoral VA ECMO can produce suboptimal coronary oxygenation in patients unable to tolerate one-lung ventilation. A left-to-right shunt using VAV ECMO can alleviate the differential hypoxia.