Protein adsorption to biomaterials is critical in determining their suitability for specific applications, such as implants or biosensors. Here, we show that surface nanoroughness can be tailored to control the covalent binding of proteins to plasma-deposited polyoxazoline (PPOx). Nanoengineered surfaces were created by immobilizing gold nanoparticles varying in size and surface density on PPOx films. To keep the surface chemistry consistent while preserving the nanotopography, all substrates were overcoated with a nanothin PPOx film. Bovine serum albumin was chosen to study protein interactions with the nanoengineered surfaces. The results demonstrate that the amount of protein bound to the surface is not directly correlated with the increase in surface area. Instead, it is determined by nanotopography-induced geometric effects and surface wettability. A densely packed array of 16 and 38 nm nanoparticles hinders protein adsorption compared to smooth PPOx substrates, while it increases for 68 nm nanoparticles. These adaptable surfaces could be used for designing biomaterials where proteins adsorption is or is not desirable.