As an alternative method to conventional split-thickness skin grafts (STSGs), we recently proposed fractional skin grafting (FSG), which consists in harvesting hundreds of microscopic skin tissue columns (MSTCs) to place them directly into the skin wound (Tam et al., 2013, “Fractional Skin Harvesting: Autologous Skin Graft Without Donor Site Morbidity,” Plast. Reconstructive Surgery–Global Open, 1(6)). This paper (i) introduces the concept and operational principles of a simple but robust fractional skin harvesting (FSH) device and (ii) presents the quantitative evaluation of the deployment of the FSH device with respect to different harvesting-needle sizes. The device utilizes a hypodermic needle with a specific cutting-geometry to core skin tissue mechanically. The tissue core is removed from the donor site into a collecting basket by air and fluid flows. The air flow transports the tissue core, while the fluid flow serves the purpose of lubrication for tissue transport and wetting for tissue preservation. The design and functionality of the device were validated in an animal study conducted to establish preclinical feasibility, safety and efficacy of the proposed FSH device and FSG method. The FSH device, operating at 55.16 kPa (8 psi) gauge pressure and 208 ml/min saline flow rate, cored 800 μm diameter × 2.5 mm length skin columns using a 1.05/0.81 mm outer/inner diameter needle. The MSTC harvesting rate was established by the user at 1 column/sec. For this columns size, about 50 MSTCs are required to cover a 1.5 cm × 1.5 cm wound. In comparison to STSGs, the proposed FSG method results in superior healing outcomes on the donor and wound sites. Most important, the donor site heals without morbidity by remodeling tissue, as opposed to scarring. The FSH device has the capability of extracting full-thickness skin columns while preserving its viability and eliminating the donor site morbidity associated with skin grafting.