The optimal concentration of mafenide acetate solution for use in the treatment of burns is unknown. Despite data supporting the use of a 2.5% solution, 5% formulation is traditionally used, and has been the highest-costing medication on formulary. The aim of the current study is to evaluate cost and patient outcomes associated with a new policy implementing the use of 2.5% solution in burn patients and restricting the 5% formulation to specific indications only. A retrospective review of all patients receiving mafenide acetate solution at a single pediatric burn hospital was performed before and after the initiation of the new policy on the use of 5 vs 2.5% solution. Duration of therapy, adverse events, cost, incidence of wound infection, and bacteremia were analyzed. In 2009, 69 patients were treated with 5% mafenide acetate solution for a total cost of $125,000 ($1811 per patient). In 2010, after the initiation of the policy, 48 patients were treated: 19 received 5% mafenide acetate solution with appropriate indication, whereas the remaining 29 received 2.5% solution for a total cost of $38,632 ($804 per patient). There were no significant changes in the incidence of bacteremia or wound infection. No side effects of either solution were noted. Under certain conditions, a 2.5% mafenide acetate solution appears sufficient. In this multinational pediatric burn hospital, the use of a 2.5% solution was not associated with increased bacteremia or wound infection, and proved to be more cost-effective.