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Artificial lung (AL) membranes are used for blood oxygenation for patients undergoing open-heart surgery or acute lung failures. Current AL technology employs polypropylene and polymethylpentene membranes. Although effective, these membranes suffer from low biocompatibility, leading to undesired blood coagulation and hemolysis over a long term. In this work, we propose a new generation of AL membranes based on amphiphobic fluoropolymers. We employed poly­(vinylidene-co-hexafluoropropylene), or PVDF-co-HFP, to fabricate macrovoid-free membranes with an optimal pore size range of 30–50 nm. The phase inversion behavior of PVDF-co-HFP was investigated in detail for structural optimization. To improve the wetting stability of the membranes, the fabricated membranes were coated using Hyflon AD60X, a type of fluoropolymer with an extremely low surface energy. Hyflon-coated materials displayed very low protein adsorption and a high contact angle for both water and blood. In the hydrophobic spectrum, the data showed an inverse relationship between the surface free energy and protein adsorption, suggesting an appropriate direction with respect to biocompatibility for AL research. The blood oxygenation performance was assessed using animal sheep blood, and the fabricated fluoropolymer membranes showed competitive performance to that of commercial polyolefin membranes without any detectable hemolysis. The data also confirmed that the bottleneck in the blood oxygenation performance was not the membrane permeance but rather the rate of mass transfer in the blood phase, highlighting the importance of efficient module design.