The aim of this study is to histologically characterize the wound healing process of in vivo human skin treated with 1064- and 532-nm microlens array (MLA)-type picosecond lasers. Three patients (Fitzpatrick skin types II-IV), who were undergoing future cosmetic abdominoplasties, were treated with 1064- and 532-nm MLA-type lasers under different fluence settings. Treatments were performed 2 weeks, 1 week, and immediately prior to surgery. Skin samples were harvested from the resected tissue with 8 mm punch biopsies immediately after the abdominoplasties were performed. The study demonstrates that intraepidermal vacuoles, created from tissue damage induced by the laser, are histologically resolved within 1 week without persistent damage to the dermoepidermal junction or vasculature. After 2 weeks, all foci of microscopic epidermal necrotic debris had either resolved or migrated to more superficial levels in the stratum corneum. There was no evidence of persistent vascular damage, increased melanophages, or accumulation of melanin in the dermis at 2 weeks. Furthermore, the 1064-nm picosecond laser with the high fluence setting demonstrated the capacity to fractionally ablate the epidermis and induce multifocal fibrosis in the papillary dermis in lighter skin types. This is the first study to demonstrate the wound healing profile of in vivo human skin after treatment with the picosecond 1064- and 532-nm MLA-type lasers. It shows that laser-induced tissue damage is histologically resolved within 2 weeks, clinically reflecting a favorable safety profile and short downtime. The study also shows that the picosecond laser can be used to induce either fractional ablative or non-ablative effects, depending on the fluence settings used. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.