Background: Recirculation during veno-venous extracorporeal membrane oxygenation reduces extracorporeal oxygen exchange and patient oxygenation. To minimize recirculation and maximize oxygen delivery (DO2) the interaction of cannulation, ECMO flow and cardiac output requires careful consideration. We investigated this interaction in an ... observational trial. Methods: In 19 patients with acute respiratory distress syndrome and ECMO, we measured recirculation with the ultrasound dilution technique and calculated extracorporeal oxygen transfer (VO2), extracorporeal oxygen delivery (DO2) and patient oxygenation. To assess the impact of cardiac output (CO), we included CO measurement through pulse contour analysis. Results: In all patients, there was a median recirculation rate of approximately 14–16%, with a maximum rate of 58%. Recirculation rates >35% occurred in 13–14% of all cases. In contrast to decreasing extracorporeal gas exchange with increasing ECMO flow and recirculation, patient oxygenation increased with greater ECMO flows. High CO diminished recirculation by between 5–20%. Conclusions: Extracorporeal gas exchange masks the importance of DO2 and its effects on patients. We assume that increasing DO2 is more important than reduced VO2. A negative correlation of recirculation to CO adds to the complexity of this phenomenon. Patient oxygenation may be optimized with the direct measurement of recirculation.