Control of wound infections, especially those associated with methicillin-resistant Staphylococcus aureus, is necessary for the wound healing process. Selection of topical agents should be based not only on their ability to eliminate pathogenic bacteria, but also on whether they may be detrimental to tissue repair. Two randomized, controlled in vivo studies using different porcine models were conducted to evaluate the effect of a topical oak bark ointment (treatment) on 1) methicillin-resistant Staphylococcus aureus in partial-thickness wounds, and 2) healing of second-degree burn wounds. Silver sulfadiazine, oak bark ointment vehicle control (polyethylene glycol), and no treatment (untreated wounds) were used as controls in both studies. In the first study, 108 partial-thickness wounds in three animals were inoculated with a methicillin-resistant S. aureus suspension (average 6.96+/-0.4 log CFU/mL) and covered for 24 hours with a polyurethane film. After polyurethane film removal, treatments were applied twice daily and nine wounds per day (three per animal) from each treatment group were cultured after 24, 48, and 72 hours. Methicillin-resistant S. aureus colonization was lowest in the active treatment group at all three assessment times and after 72 hours ranged from (5.01+/-1.1 CFU/mL) in the treatment to (6.20+/-0.8 CFU/mL) in the vehicle control treated wounds. In the second study, treatments were applied twice daily to second-degree burn wounds (n = 720) on eight animals. Daily epithelialization assessment (n = five wounds) was performed on day 7 through 10 after wounding. At every assessment time, the proportion of wounds healed was higher in the treatment than in the control treatment groups - days 8, 9, and 10 (active versus vehicle and untreated), P <0.01; days 9 and 10 (vehicle versus untreated), P <0.001. The oak bark formulation studied reduces methicillin-resistant S aureus contamination and facilitates healing in vivo. Research to ascertain the importance of these findings for clinical practice is needed.