Mafenide acetate is an antimicrobial agent used to decrease the bacterial load for burn wounds. The 5% solution is more commonly used yet double the cost of its 2.5% counterpart. This study aims to evaluate outcomes and cost associated with the use of 2.5 vs 5% mafenide acetate formulation in the adult burn population. Adult patients (≥18 years) receiving 2.5% mafenide acetate during an 11-month period between 2014 and 2015, corresponding to a policy change in favor of the use of 2.5% mafenide acetate, were queried. Historical controls, patients receiving 5% mafenide acetate, were also reviewed during an 11-month period between 2013 and 2014. A retrospective review was performed comparing wound infection rate, bacteremia, sepsis, pneumonia, duration of mafenide therapy, length of hospital stay, mortality, and cost. A total of 54 and 65 patients received 2.5 and 5% mafenide acetate, respectively. There was no difference in wound infection, bacteremia, sepsis, pneumonia, duration of treatment, and mortality between the two groups. No adverse events occurred in either group directly related to mafenide. Candida and Staph species were the two most common isolates in the 2.5% group, whereas Pseudomonas and Staph species were the most common in the 5% arm. The mean cost of 2.5% mafenide therapy was $1494.92 compared with $3741.39 for 5% mafenide acetate. The 2.5% concentration demonstrates to be an equally efficacious and cost-effective alternative to the 5% concentration. Burn centers should consider the use of the more dilute preparation for burn wound infection prophylaxis as it may reduce the cost without compromising patient safety.