The management of split-thickness skin graft donor sites is targeted towards promoting the healing process, while minimizing adverse effects and complications. The aim of this study was to compare donor site treatment outcome between Aquacel, a carboxymethylcellulose-based hydrofiber dressing, and the standard mesh paraffin gauze dressing. The study included 23 adult patients. Half of the skin graft donor site in the proximal thigh was dressed with paraffin gauze and the rest with Aquacel. The results indicated that patients treated with Aquacel experienced significantly less pain and a more rapid rate of epithelialization compared with patients treated with mesh paraffin gauze dressing. Final scarring (ie, after the 1-year follow-up) was significantly better with the Aquacel dressing. We conclude that Aquacel dressing is superior to the standard mesh paraffin gauze dressing for split-thickness donor site area in pain relief, ease of treatment, promotion of epithelialization, and the quality of scarring.