Skin is the most commonly used tissue for the transplantation. A meticulous care of the donor site is needed to prevent scarring, delayed healing, and pain. Various agents and dressing materials have been reported to help healing of skin graft donor sites. Sucralfate is an extensively used agent, which provides acute gastroprotection and acceleration of chronic ulcer healing. In this study, we assessed the effects of topical sucralfate on the healing of the split thickness skin graft donor sites in a prospective comparative way. The study was carried out on 32 randomly chosen patients undergoing surgery for various causes and requiring split thickness skin graft resurfacing. The upper halves of the skin graft donor sites on the thighs were simply covered with paraffin gauze and the lower half was covered with sucralfate-soaked paraffin gauzes. The day of full epithelization varied from 6 to 9 days and 8–12 days on the sucralfate-applied areas and on the control sites, respectively. The mean value of the healing was 7.01 days in the studied lower halves and 10.8 days in the upper halves. The healing rate was strikingly faster and less painful on the sucralfate-applied areas. We were able to discharge patients earlier than usual, and patients’ comfort increased. It seems that sucralfate is a promising topical agent to increase the healing rate and decrease the incidence of associated problems such as pain and hypertrophic scar.