Background This randomized, open-label study evaluated Aquacel Ag ® Hydrofiber ® dressing with silver (HDS; ConvaTec, Skillman, NJ, USA) with an adherent or gelled protocol in the management of split-thickness donor sites. Methods HDS was the primary dressing in the adherent group (gauze as secondary covering) and gelled group (transparent film as secondary covering). Dressings were changed on study day 1 or 2 and study days 5 (optional), 10 (optional), and 14. The primary outcome was healing (≥90% re-epithelialization) at study day 14. Results Seventy subjects were treated (36 adherent, 34 gelled). By study day 14, 77% of donor sites had healed (67% adherent, 88% gelled). Pain scores decreased over time in both treatment groups. Investigators were “very satisfied” or “satisfied” with (adherent, gelled) time required to manage dressing change (89%, 79% of subjects), minimization of donor-site pain (64%, 82%), ease of application (97%, 94%), management of drainage (92%, 82%), ease of removal (77%, 85%), and ability of dressing to remain in place (69%, 76%). Thirty-nine (56%) subjects had adverse events, most commonly non-donor-site infection (11%) and gastrointestinal events (11%). Conclusion In this randomized, open-label study, HDS was well-tolerated, versatile, and effective in the management of split-thickness donor sites.