We report that during VV-ECMO, PP improved oxygenation without a change in respiratory system compliance and PaCO2 at constant levels of minute ventilation and sweep gas flow. This does not suggest lung recruitment by PP but rather an optimization of ventilation and perfusion matching. Three explanations could be advanced for the mortality rate in the prone ECMO group (78.6%). First, prone ECMO patients may be more severe than supine ECMO patients. As described by Gattinoni et al., worsening patients progress from type 1 to type 2 (higher percentage of non-aerated tissue) [1], which is associated with a higher mortality rate [4]. Prone ECMO patients had much more consolidations, obviously because ECL was the main indication to be prone (n = 10/14). Furthermore, prone ECMO patients need a higher respiratory rate for a higher sweep gas flow suggesting that they may be exposed to a higher mechanical power, and they possibly had also a higher dead space. Second, postmortem biopsies, performed in 6 patients with ECL in the prone ECMO group, found a fibrin exudative presence both in the alveolar spaces and bronchioles followed by a fibroblastic phase [5] and raise the question of the use of corticosteroids (only one patient in the prone ECMO group). Third, as already described by Zeng et al. [6], more than half (8/11) of the patients died from septic shock and multiple organ failure, for which ECMO may be useless.