Vascular surgical site infection (SSI) is caused by pathogenic bacterial strains whose preferred mode of growth is within a surface biofilm. Bacterial biofilm formation can develop within hours to days in a wound and produces a recalcitrant infectious process especially in the presence of a prosthetic graft. The initial steps of biofilm formation are bacterial adhesion to biologic or inert surgical site structures followed by organism production of exopolysaccaride matrix which encases developing bacteria colonies to produce a protective microenvironment. As the biofilm matures, a dynamic process of organism cell-to-cell signaling occurs with varying growth modes of sessile bacteria within the biofilm and the release of planktonic bacteria with the potential to spread and expand the biofilm-mediated infection. The prevalence of staphyloccocal strains causing vascular SSI is best understood when viewed as a biofilm-mediated infection with virulence factors related to specific cell surface adhesion proteins and bacteria-derived matrix production. Nonhealing surgical sites following lower limb revascularization, the late appearance of prosthetic graft infection caused by Staphylococcus epidermidis, and the development of groin site tracts after aortofemoral bypass grafting are clinical examples of a biofilm-mediated SSI. A mature biofilm within a wound or coating a prosthetic device exhibits resistance to host defenses and selected antibiotics, impairs wound healing, and is a perpetual irritant to that host by inciting a chronic inflammatory process. By understanding the microbial pathogenesis of biofilm formation, strategies to treat and prevent biofilm-mediated infection can be developed and utilized to reduce vascular SSIs.