The efficacy of drug delivery and other nanomedicine-related therapies largely relies on the ability of nanoparticles to reach the target organ. However, when nanoparticles are injected in the bloodstream, their surface is instantly modified upon interaction with blood components, principally with proteins. We know that a dynamic and multi-layered protein structure is formed spontaneously on the nanoparticle upon contact with physiological media, which has been termed protein corona. Although several determinant factors involved in protein corona formation have been identified from in vitro studies, specific relationships between the nanomaterial synthetic identity and its ensuing biological identity under realistic in vivo conditions remains elusive. We present here a detailed study of in vivo protein corona fromation after blood circulation of anisotropic gold nanoparticles (nanorods and nanostars). Plasmonic gold nanoparticles of different shapes and sizes were coated with polyethyleneglycol, intravenously administered in CD-1 mice and subsequently recovered. The results from gel electrophoresis and mass spectrometry analysis revealed the fromation of complex protein coronas, as early as 10 minutes post-injection. The toal amount of protein adsorbed onto the particle surface, as well as the protein corona composition were found to be affected by both particle size and shape.