Three consecutive studies were performed in 58 patients evaluating the effect of occlusion on the healing of partial-thickness wounds. Mirror-image donor sites were covered with the occlusive hydrocolloid dressing (HCD) (DuoDermIN) and compared to fine mesh gauze, and the HCD was subsequently compared to a semi-occlusive dressing of polyurethane film, (Op-siteIN). In addition, partial-thickness burn wounds were covered with the HCD and the remaining burn wound was treated with silver sulfadiazine. The donor sites and burn wounds treated with HCD healed significantly faster than those covered with fine mesh gauze or silver sulfadiazine (p < 0.001) and with less pain. The HCD and polyurethane film were equivalent. There were no clinical infections with the wounds that were occluded. The exudate collected beneath the DuoDerm and Op-site on donor sites was added to the tissue culture system and resulted in a modest increase in keratinocyte proliferation. However, the exudate from burn wounds under HCD resulted in a marked increase in cell proliferation (p < 0.001).