Surgical and endovascular therapies for severe atherosclerosis often fail due to the development of neointimal hyperplasia and arterial restenosis. Our objective was to synthesize, characterize, and evaluate the targeting specificity and biocompatibility of a novel systemically injected nanoparticle. We hypothesize that surface-functionalization of gold nanoparticles (AuNPs) with a collagen-targeting peptide will be biocompatible and target specifically to vascular injury. 13 nm AuNPs were surface functionalized with a peptide-molecular fluorophore and targeted to collagen (T-AuNP) or a scrambled peptide sequence (S-AuNP). After rat carotid artery balloon injury and systemic injection of T-AuNP or S-AuNP, arteries and organs were harvested and assessed for binding specificity and biocompatibility. The T-AuNP bound with specificity to vascular injury for a minimum of 24 h. No significant inflammation was evident locally at arterial injury or systemically in major organs. The T-AuNP did not impact endothelial cell viability or induce apoptosis at the site of injury in vivo. No major changes were evident in hepatic or renal blood chemistry profiles. Herein, we synthesized a biocompatible nanoparticle that targets to vascular injury following systemic administration. These studies demonstrate proof-of-principle and serve as the foundation for further T-AuNP optimization to realize systemic, targeted delivery of therapeutics to the sites of vascular injury.