The stratum corneum and epidermal pigmentation have protective roles against ultraviolet radiation. Because vitiligo skin lacks melanocytes and has no potential to produce pigment, some studies suggested that the epidermis in vitiligo skin is thicker than in normal skin. However, only a few studies investigated epidermal thickness changes in vitiligo, and some of these had relatively small sample sizes. Thus, this study aimed to compare epidermal thickness between vitiligo skin and adjacent normal-appearing skin in a large cohort. Photos of hematoxylin and eosin–stained slides of vitiligo skin and adjacent normal-appearing skin were taken under a microscope. The thicknesses of the stratum corneum, viable epidermis, and full epidermis were then measured by a computerized image analyzer. A total of 206 patients (412 sections) were included. There were significant differences between vitiligo skin and adjacent normal-appearing skin in the thickness of the stratum corneum (P = 0.009), viable epidermis (P = 0.001), and total epidermis (P = 0.001). An analysis comparing skin biopsied from a sun-exposed area versus a sun-protected area showed that the stratum corneum, viable epidermis, and total epidermis were significantly thicker in vitiligo skin than in normal-appearing skin in sun-exposed areas (P < 0.05), but not in sun-protected areas. We revealed that the epidermis was thicker in vitiligo skin than in normal-appearing skin, especially on sun-exposed skin, and that this may represent a photoprotective role compensating for absent pigmentation.