The clinical use of veno-venous extracorporeal membrane oxygenation (VVECMO) in adult patients with respiratory failure is rapidly increasing. However, recirculation of blood oxygenated by ECMO back into the circuit may occur in VVECMO, resulting in insufficient oxygenation. The cannula position and bypass flow rate are two major factors influencing recirculation, but the relationship and ideal configuration of these factors are not fully understood. In the present study, we attempted to clarify these parameters for effective gas exchange. VVECMO was performed in eight adult goats under general anesthesia. The position of the drainage cannula was fixed in the inferior vena cava (IVC), but the return cannula position was varied between the IVC, right atrium (RA), and superior vena cava (SVC). At each position, the recirculation rates calculated, and the adequacy of oxygen delivery by ECMO in supplying systemic oxygen demand was assessed by measuring the arterial oxygen saturation (SaO2) and pressure (PaO2). Although the recirculation rates increased as the bypass flow rates increased, SaO2 and PaO2 also increased in any position of return cannula. The recirculation rates and PaO2 were 27 ± 2% and 162 ± 16 mmHg, 36 ± 6% and 139 ± 11 mmHg, and 63 ± 6% and 77 ± 9 mmHg in the SVC, RA and IVC position at 4 L/min respectively. In conclusion, the best return cannula position was the SVC, and a high bypass flow rate was advantageous for effective oxygenation. Both the bypass flow rates and cannula position must be considered to achieve effective oxygenation.