Injectable surgical sealants and adhesives, such as biologically derived fibrin gels and synthetic hydrogels, are widely used in medical products. While such products adequately adhere to blood proteins and tissue amines, they have poor adhesion with polymer biomaterials used in medical implants. To address these shortcomings, we developed a novel bio-adhesive mesh system utilizing the combined application of two patented technologies: a bifunctional poloxamine hydrogel adhesive and a surface modification technique that provides a poly-glycidyl methacrylate (PGMA) layer grafted with human serum albumin (HSA) to form a highly adhesive protein surface on polymer biomaterials. Our initial in vitro tests confirmed significantly improved adhesive strength for PGMA/HSA grafted polypropylene mesh fixed with the hydrogel adhesive compared to unmodified mesh. Toward the development of our bio-adhesive mesh system for abdominal hernia repair, we evaluated its surgical utility and in vivo performance in a rabbit model with retromuscular repair mimicking the totally extra-peritoneal surgical technique used in humans. We assessed mesh slippage/contraction using gross assessment and imaging, mesh fixation using tensile mechanical testing, and biocompatibility using histology. Compared to polypropylene mesh fixed with fibrin sealant, our bio-adhesive mesh system exhibited superior fixation without the gross bunching or distortion that was observed in the majority (80%) of the fibrin-fixed polypropylene mesh. This was evidenced by tissue integration within the bio-adhesive mesh pores after 42 days of implantation and adhesive strength sufficient to withstand the physiological forces expected in hernia repair applications. These results support the combined use of PGMA/HSA grafted polypropylene and bifunctional poloxamine hydrogel adhesive for medical implant applications.