Incisional hernia continues to be a common complication of hernia repair in spite of the development of various synthetic and bio-synthetic repair materials. Poor long-term mechanical strength, leading to high recurrence rates, has limited the use of acellular dermal matrices (ADM) in ventral hernia repair (VHR). Biologically-derived meshes have been an area of increasing interest, but these materials bring the risk of more aggressive immune response and fibrosis in addition to the mechanical failures suffered by synthetic materials. Platelet rich plasma (PRP), a growth factor rich autologous blood product, has been shown to improve early neovascularization, tissue deposition, and to decrease rates of recurrence. Here, we demonstrate that platelet-rich plasma promotes release of growth factors SDF-1, TGFβ, and PDGF in a dose-dependent manner. Additionally, we show that platelet-rich plasma promotes angiogenesis both in vitro and in vivo, corresponding with increased expression of VEGF and COL1a. Finally, we show that the molecular and cellular activity initiated by platelet-rich plasma results in increased mechanical stiffness of the hernia repair mesh over time. Collectively, these data represent an important step in demonstrating the utility and the mechanism of platelet-derived plasma in biomaterial-aided wound healing and provide promising pre-clinical data that suggest such materials may improve surgical outcomes. The data below in two Excel sheets and three Prism files contain the raw data for our in vitro and in vivo experiments.