Aims Hydrogen peroxide (H2O2) disinfection applications are limited by its rapid inactivation. The aims of this study were to (i) micro-encapsulate H2O2 in silica hydrogels to obtain controlled release up to 72 h, (ii) test hydrogel antimicrobial activity against four common pathogens and (iii) assess H2O2 release kinetics and antimicrobial activity in 35-65% relative humidity and 37 degrees C to approximate bandaged wound conditions. Methods and Results Hydrogels were characterized using scanning electron microscopy, nitrogen sorption porosimetry, Brunauer Emmet Teller analysis and the Barret-Joyner-Halenda method. Hydrogels formed at lower pH demonstrated increased surface area and decreased pore size, resulting in H2O2 release lasting 72 h. Using agar well diffusion for antimicrobial activity, statistically significant zones of inhibition (as compared to controls) were seen for Escherichia coli, Staphylococcus aureus, Pseudomona aeruginiosa and Vancomycin-resistant Enterococcus faecalis. Activity remained for hydrogels aged for 72 h in humid, 37 degrees C conditions. Conclusions Hydrogels can be synthesized to provide a continuous, controlled release of H2O2 for up to 72 h. Significance and Impact of the Study: Stable, controlled-release H2O2 hydrogels have potential applications for wound treatment and disinfection of medical equipment, through bonding to bandages or materials such as catheter lumens.