BACKGROUND: Most often, the natural form of vitamin A (retinol palmitate) is used to prevent skin aging. There are two topical preparations in the form of ointment on the Russian market that contain a high concentration of retinol palmitate, including in combination with cholecalciferol and tocopherol acetate. The specific effects of these drugs on the structure of aging skin have not yet been fully studied. AIM: Comparative histological assessment of the effect of topical preparations in the form of ointment containing retinol palmitate on the epidermis and dermis of women aged 40–55 years. MATERIALS AND METHODS: The clinical study included 18 women aged 40 to 55 years old. Group 1 included 6 women who used retinol palmitate ointment 2 times a day on the skin of the face. Group 2 consisted of 6 women who used the dermatoprotective agent 2 times a day on the skin of the face which, in addition to retinol palmitate, includes cholecalciferol and α-tocopherol acetate. Group 3 consisted of 6 women and was an intact comparison group. The observation period is 90 days. Patients underwent a punch biopsy with histological examination of the skin before and after the observation period. RESULTS: According to the results of the study, it was revealed that ointments with a high concentration of retinol palmitate have a stimulating effect on the proliferation of keratinocytes of the epidermis, which manifested itself in an in increasing the number of rows of cells of the prickly layer. In addition, under the action of these drugs, the synthetic activity of keratinocytes of the granular layer increases, which contributes to the proper formation of the stratum corneum of the epidermis. The use of ointments leads to a significant increase in the thickness of both the granular and prickly layers of the epidermis and the dermis. CONCLUSION: Ointments with a high concentration of retinol palmitate improve the structure of aging skin.