Background/purpose: Incidence of skin complications in ostomy patients constitutes a well‐known and well‐described problem. The reasons are, however, very difficult to describe because of the many factors contributing to the problem. This article describes the skin changes derived exclusively from the adhesives used in a carefully controlled, long‐term study using two fundamentally different types of adhesives: a hydrocolloid adhesive and a zinc oxide adhesive. Methods: The adhesives were changed daily on the volar forearm of 11 volunteers for a 4‐week period. Once a week, transepidermal waterloss (TEWL), water content of the skin, erythema and the peel force applied for removal of the adhesives were measured. On the last day of the study, a replica of the skin surface was obtained to determine changes in the skin topography, and a biopsy was taken to study changes at the cellular level. Results and conclusion: We found increased TEWL and decreased water content in skin treated with the zinc oxide adhesive, but increased waterloss and water content when the hydrocolloid adhesive was used. In addition, the area treated with zinc oxide adhesive showed significant increase of epidermal thickness, scaly appearance and parakeratosis with similarities to pathological dry skin diseases such as psoriasis and atopic dermatitis, changes that were not found when using the hydrocolloid adhesive. The skin response seems to be the result of the content of zinc oxide and the mechanical interaction of the zinc oxide adhesive. We conclude that the nature of the adhesive plays an important role in the skin response to repeated application of adhesives, as seen in peristomal skin.