Introduction The main manifestation of COVID-19 pneumonia is acute respiratory distress syndrome (ARDS), which in some cases can be more severe, requiring Veno-venous extracorporeal membrane oxygenation (VV-ECMO) to ensure hemostasis. Despite support from Veno-venous extracorporeal membrane oxygenation, some patients may remain hypoxemic. One possible therapeutic procedure for these patients is the application of the prone position (PP). Objective The aim of this study was to investigate the effect of VV-ECMO on arterial oxygenation and compliance of the respiratory system in mechanically ventilated patients with refractory hypoxemia. The secondary objective was to evaluate the safety and feasibility of prone position for ECMO. Methods We retrospectively reviewed the electronic records of all 23 COVID-19 patients on ECMO who were placed for the first time in prone position with an average duration of 16 h. Patient characteristics, pre-ECMO characteristics, changes in ventilator/ECMO settings and blood gas analysis before and after PP. Results A total of 23 position changes to prone position were performed. Oxygenation and respiratory compliance improved 16 h after adoption of prone position without any accidents during PP. Conclusions The use of prone position during Veno-venous extracorporeal membrane oxygenation demonstrated an improvement in oxygenation as well as lung compliance. It is a safe and reliable technique.