Animal models are invaluable tools for translational research, allowing investigators to recapitulate observed clinical scenarios within the laboratory that share attributes with human disease. Here, we describe a mouse model of post-arthroplasty Staphylococcus epidermidis joint infection which mimics human disease and may be utilized to explore the complex series of events during staphylococcal implant-associated infections by identifying key immunological, bacterial, and/or therapeutic mechanisms relevant to these persistent infections.