We evaluated a novel octylcyanoacrylate-based liquid occlusive dressing for partial-thickness wounds. One hundred and fifteen standardized wounds were created with an electric dermatome set at a depth of 600 micro on the flanks of three pigs and randomly treated with liquid occlusive dressing, a hydrocolloid dressing, or gauze. In one pig, wounds were swabbed with Staphylococcus aureus. Biopsies were taken after 4, 5, 6, and 21 days. Hemostasis was obtained in all wounds treated with the liquid occlusive. The percent reepithelialization of wounds treated with the liquid occlusive and hydrocolloid dressings were significantly greater at days 4 and 5 than control wounds (78% and 82% vs. 40%, p < 0.001 and 99% and 100% vs. 72%, p < 0.001, respectively). None of the liquid occlusive-treated wounds challenged with bacteria became infected. Foreign body reactions were least common in wounds treated with the liquid occlusive (p < 0.001). Scar depth was less for liquid occlusive- and hydrocolloid-treated wounds than controls (285 micro and 303 micro vs. 490 micro, p < 0.001). We conclude that excisional wounds treated with the liquid occlusive dressing reepithelialize as quickly as hydrocolloid-treated wounds. The liquid occlusive dressing is an effective microbial barrier and hemostatic agent resulting in fewer foreign body reactions than hydrocolloid-treated wounds or controls.