The authors verified the excellent antithrombogenicity of a blood-liquid interface (BLI) and introduced an oxygenator based on the principle of gas exchange across direct BLI. In a newly developed oxygenator, three layers of liquid flowed horizontally, contacting one another: O2 saturated silicone oil on the top, O2 saturated fluorcarbon at the bottom, and blood in the middle. Gas exchange was carried out across both direct BLIs. This system provided excellent antithrombogenicity as well as good gas exchange. The results indicate that this method will become a promising modality for prolonged extracorporeal oxygenation.