This study was conducted to identify the causes of plasma leakage of oxygenators in extra corporeal membrane oxygenation (ECMO). From 1996 through 2002, 91 oxygenators were used in 62 patients undergoing ECMO for respiratory and/or cardiac failure. Several types of oxygenators were used (Medtronic Maxima, Minima, PRF, Medos Hilite). Patient variables and variables related to the ECMO set-up were analysed for their relationship with oxygenator failure by a time related multiple regression analysis (Cox). Oxygenator failure occurred in 26% of the cases. The analysis identified the type of oxygenator (p=0.0016), younger patient age (p=0.04) and the number of oxygenators used (p=0.03) as the independent significant risk factors. The type of oxygenator used has the most overwhelming effect (significantly less leakage with the Medos Hilite). In conclusion, leakage of oxygenators is predominantly caused by the type of oxygenator used. Patient variables (younger age and the number of oxygenators used in one patient) are also significant and allude to an inflammatory process as underlying mechanism of plasma leakage.