Extracorporeal membrane oxygenation (ECMO) is currently the only life support system for acute lung failure. Consistent gas permeability is of crucial importance for optimal device function, and its longterm operation is hampered by the successive binding of proteins, and thrombocytes to the surface of the oxygenators leading to thrombus formation and necessitating repeated device replacement, further endangering patients’ lives. In this project, protein adsorption on non-coated or heparin-coated oxygenator membranes was analysed over time. Initially, miniature devices were created and analysed after blood and plasma contact and later compared to used patient oxygenators. Data from miniature oxygenators showed stronger remodelling of the protein layer on non-coated membrane surfaces. Heparin-coating initially altered the protein adsorption towards anti-coagulant and complement inhibitory proteins. However, after 6 hours, the positive effect was diminished. We demonstrated that initiator components of the classical and lectin complement pathways were bound but not the further executing complement components of these pathways. Hence, complement system activation occurred via the alternative pathway. A combined coating of hollow fibre membranes with heparin and the complement inhibitor protein, C1-esterase inhibitor, significantly reduced the early activation of the contact phase. Based on the obtained data, additional oxygenator coatings are currently under investigation to further improve the anti-thrombotic properties of oxygenator membranes. Furthermore, we investigated the influence of flow rates and material (gas exchange vs. heat exchange) in vitro and identified the higher flow rates as the most important factor of increased protein adsorption in miniature devices. Analyses of patient oxygenators was performed as part of the project. The oxygenators used for female patients exhibited increased protein adsorption, and a longer application time was responsible for increased protein adsorption to membranes. However, no differences were observed between the initial oxygenators or subsequent replacement oxygenators, indicating that the protein layers formed on the membranes develop similarly also with subsequent oxygenator devices. A comparison with the oxygenators used by Covid-19 patients clearly showed significantly increased binding of proteins of the complement system, platelet activation, and leukocyte transendothelial migration compared to non-Covid oxygenators. In summary, this project provided a detailed analysis of the blood proteins adhering to the oxygenators, which will contribute to a better understanding of the interactions and the development of novel coatings to improve the hemocompatibility of artificial lungs.