Autologous platelet-rich plasma contains multiple growth factors. We performed a side-by-side (half-side) test between the platelet-rich plasma (PRP)-treated and control (untreated) sides of a split-thickness skin graft donor site, and compared the number of days until epithelialization and pain during gauze change. On day 13 after surgery, we performed punch biopsy on the two sides and for adjacent normal skin tissue and compared the epidermal thickness and numbers of collagen fibers and newly formed vessels in the dermis by H&E staining, elastica van Gieson staining, and α-smooth muscle actin (α-SMA) immunostaining. Epithelialization progressed more rapidly, pain during gauze change was milder, and the epidermal thickness and number of newly formed vessels in the dermis were significantly greater on the PRP-treated side. This study revealed that PRP promotes epithelialization and angiogenesis of split-thickness skin graft donor sites.