Mafenide acetate is used in some burn wounds for its ability to penetrate eschar but requires frequent uncomfortable dressing changes for its application. The authors hypothesize that hydrofiber dressings will hold mafenide acetate solution for an extended period of time and maintain antimicrobial activity longer than traditional gauze, thus possibly obviating the need for frequent dressing changes. Four experimental arms included: 1) hydrofiber, stored on a dry well plate as control, 2) gauze saturated with 2.5% mafenide acetate, stored on nonsterile porcine skin, 3) hydrofiber saturated with mafenide acetate, stored on dry well plate, and 4) hydrofiber saturated with mafenide acetate, stored on nonsterile porcine skin. At 0, 24, 48, and 72 hours, a 1-cm disk was cut from the dressing sheet of each study arm, placed on agar plates seeded with Staphylococcus aureus and Pseudomonas aeruginosa, and incubated for 24 hours, and the zone of inhibition was measured. A zone of 2 mm or greater was indicative of susceptibility. Each arm of the experiment was performed four times to demonstrate reproducibility. Plain hydrofiber (control) demonstrated no zone of inhibition at any time point, thereby possessing no antimicrobial activity alone. Gauze saturated with mafenide acetate did not reliably demonstrate antimicrobial activity beyond 0 hours. Hydrofiber saturated with mafenide acetate, whether stored on a dry well plate or nonsterile porcine skin, consistently possessed sustained antimicrobial activity as demonstrated by zones of inhibition greater than 2 mm to both S. aureus and P. aeruginosa. Mafenide acetate-soaked hydrofiber dressings stay moist and maintain antimicrobial activity against S. aureus and P. aeruginosa for at least 72 hours without repeated soaks.