Tissue engineering has been widely applied in recent years in the treatment of skin disorders, for which the fabrication of scaffolds with layered and three-dimensional (3D) structures has received much attention. Herein, electrospinning and electrohydrodynamic (EHD) jet printing were used to fabricate 3D nano- and microfiber poly(epsilon-caprolactone) bilayer scaffolds. Electrospinning of the fiber membranes increased the surface area of the scaffolds, which can promote cell adhesion. EHD jet printing was used to extrude microfibers to fabricate a porous 3D structure mimicking that of the skin extra cellular matrix, thus facilitating cell migration and growth. The scaffolds were characterized and in vitro experiments were conducted to assess cell viability. The results showed that the 3D bilayer scaffolds had improved porosity, mechanical strength, and wettability compared with electrospun two-dimensional scaffolds. Cell viability studies showed that human umbilical vein endothelial cells were able to attach and proliferate on 3D scaffolds, proving the cytocompatibility of the fabricated scaffolds. Thus, the scaffolds have the potential to be used in clinical settings for skin regeneration.