Background/Aims: Premature infants lack the vernix caseosa, have an incompetent stratum corneum (SC) barrier and are predisposed to infection. Use of topical agents to improve barrier function has had mixed outcomes. The aim was to determine the effect of vernix versus common barrier creams on the rate and quality of the epidermal barrier repair following controlled wounding. Methods: Minor wounds were created with (1) laser ablation in the minipig and (2) tape stripping of mother’s volar skin as a model for premature skin. Native vernix was applied to the mother’s tape-stripped skin. Treatments were no occlusion (NO), vernix and a petrolatum-based cream (PBC) in the pig, and NO, vernix, PBC, an oil-in-water cream (OWC), a semipermeable film (SP) and full occlusion (FO) in adults. Results: Outcomes for both trials were barrier recovery and skin hydration (moisture accumulation rate, MAT), initial hydration, erythema and dryness in adults. Vernix and PBC produced greater barrier repair than NO in the pig. SP produced greater recovery than NO and FO in adults. Vernix yielded greater recovery than FO and was similar to PBC, OWC and NO. Vernix had a directionally higher MAT than OWC and directionally higher initial hydration than NO. Conclusions: The findings suggest that vernix-based topical creams would be effective for the treatment of epidermal wounds and show promise to augment SC repair and maturation in infants.