Pressure ulcers (PUs) frequently occur in individuals with limited mobility including patients that are hospitalized or obese. PUs are challenging to resolve when infected by antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In this study, we investigated the potential of repurposing auranofin to treat pressure ulcers infected with MRSA. Auranofin's in vitro activity against strains of S. aureus (including MRSA) was not affected in the presence of higher bacterial inoculum (107 CFU/mL) or by lowering the pH in standard media to simulate the environment present on the surface of the skin. Additionally, S. aureus did not develop resistance to auranofin after repeated exposure for two weeks via a multi-step resistance selection experiment. In contrast, S. aureus resistance to mupirocin emerged rapidly. Moreover, auranofin exhibited a long postantibiotic effect (PAE) in vitro against three strains of S. aureus tested. Remarkably, topical auranofin completely eradicated MRSA (8-log10 reduction) in infected PUs of obese mice after just four days of treatment. This was superior to both topical mupirocin (1.96-log10 reduction) and oral clindamycin (1.24-log10 reduction), which are used to treat infected PUs clinically. The present study highlights auranofin's potential to be investigated further as a treatment for mild-to-moderate PUs infected with S. aureus.