Abstract The effect of surface modification of polystyrene latex particles on subsequent protein adsorption was investigated by photon correlation spectroscopy, sedimentation, and fluorescence anisotropy decay techniques. The surface modifiers used are a series of Pluronic triblock copolymer surfactants (PEO) a (PPO) b (PEO) a (where PEO is polyethylene oxide and PPO is polypropylene oxide). The hydrodynamic thickness of the adsorbed Pluronic copolymers is proportional to the PEO chain length a as well as the molecular weight of the surfactant, with Pluronic F108 and Tetronic 908 having the thickest layers. Undetectable protein adsorption was observed on such surfactant-coated particles. This was demonstrated by monitoring the unchanged particle size upon addition of human albumin, fibrinogen, or whole plasma, in contrast with size increase for the uncoated particles. This result was also confirmed by direct adsorption isotherm measurement using sedimentation method. Furthermore, the unchanged rotational correlation time of the protein molecules upon addition of Pluronic F108-coated polystyrene particles is also consistent with the above finding of protein resistance of the coated particles. Rotational correlation time was determined from the fluorescence anisotropy decay of an extrinsic probe, 1-pyrenesulfonyl chloride, covalently attached to the protein molecules.