Aims Effects of H2O2 producing electrochemical‐bandages (e‐bandages) on methicillin‐resistant Staphylococcus aureus colonization and biofilm removal were assessed using a porcine explant biofilm model. Transport of H2O2 produced from the e‐bandage into explant tissue and associated potential toxicity were evaluated. Methods and Results Viable prokaryotic cells from infected explants were quantified after 48 h treatment with e‐bandages in three ex vivo S. aureus infection models: (1) reducing colonization, (2) removing young biofilms and (3) removing mature biofilms. H2O2 concentration‐depth profiles in explants/biofilms were measured using microelectrodes. Reductions in eukaryotic cell viability of polarized and nonpolarized noninfected explants were compared. e‐Bandages effectively reduced S. aureus colonization (p = 0.029) and reduced the viable prokaryotic cell concentrations of young biofilms (p = 0.029) with limited effects on mature biofilms (p > 0.1). H2O2 penetrated biofilms and explants and reduced eukaryotic cell viability by 32–44% compared to nonpolarized explants. Conclusions H2O2 producing e‐bandages were most active when used to reduce colonization and remove young biofilms rather than to remove mature biofilms. Significance and Impact of Study The described e‐bandages reduced S. aureus colonization and young S. aureus biofilms in a porcine explant wound model, supporting their further development as an antibiotic‐free alternative for managing biofilm infections.