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This prospective, randomized study compared protocols of care using either AQUACEL® Ag Hydrofiber® (ConvaTec, a Bristol-Myers Squibb company, Skillman, NJ) dressing with silver (n = 42) or silver sulfadiazine (n = 42) for up to 21 days in the management of partial-thickness burns covering 5% to 40% body surface area (BSA). AQUACEL® Ag dressing was associated with less pain and anxiety during dressing changes, less burning and stinging during wear, fewer dressing changes, less nursing time, and fewer procedural medications. Silver sulfadiazine was associated with greater flexibility and ease of movement. Adverse events, including infection, were comparable between treatment groups. The AQUACEL® Ag dressing protocol tended to have lower total treatment costs ($1040 vs. $1180) and a greater rate of re-epithelialization (73.8% vs 60.0%), resulting in cost-effectiveness per burn healed of $1,409.06 for AQUACEL® Ag dressing and $1,967.95 for silver sulfadiazine. A protocol of care with AQUACEL® Ag provided clinical and economic benefits compared with silver sulfadiazine in patients with partial-thickness burns.