AbstractApolipoprotein AI (apo AI) is the major protein component of high density lipoprotein (HDL), and represents ∼1% of the total protein content of plasma. In previous work, apo AI was identified as a major component of the protein layers adsorbed from plasma to biomaterials having a wide range of surface properties. Notwithstanding such indications of the major contribution of lipoprotein interactions, these phenomena have been largely overlooked in the blood‐contacting biomaterials area. In this communication, detailed quantitative data on the adsorption of apo AI to typical “biomedical” segmented polyurethane (PU) are reported. Using radiolabeled apo AI, adsorption levels from buffer and plasma were found to be ∼0.5 and ∼0.2 μg/cm2, respectively. Albumin adsorption from plasma was comparable at about ∼0.17 μg/cm2. Since, it is unknown how much of the adsorbed apo AI is associated with HDL versus how much is in the free state, the corresponding molar quantities cannot be determined with certainty. However, if it is assumed that all of the adsorbed apo AI is free, the molar quantities adsorbed from plasma were in the ratio apo AI:albumin = 2.77, compared with 0.00063 in plasma. Immunoblot data showed similar trends with respect both to the variation in adsorbed quantity with plasma concentration and to the relative adsorbed quantities of apo AI and albumin. These data show unequivocally the very strong surface activity of apo AI and suggest that a key future focus for blood compatibility research should be lipoprotein interactions. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 109–115, 2011.