Abstract Background There is substantial interest in electrospun scaffolds as substrates for tissue regeneration and repair due to their fibrous, extracellular matrix-like composition with interconnected porosity, cost-effective production, and scalability. However, a common limitation of these scaffolds is their inherently low mechanical strength and stiffness, restricting their use in some clinical applications. In this study we developed a novel technique for 3D printing a mesh reinforcement on electrospun scaffolds to improve their mechanical properties. Methods A poly (lactic acid) (PLA) mesh was 3D-printed directly onto electrospun scaffolds composed of a 40:60 ratio of poly(ε-caprolactone) (PCL) to gelatin, respectively. PLA grids were printed onto the electrospun scaffolds with either a 6 mm or 8 mm distance between the struts. Scanning electron microscopy was utilized to determine if the 3D printing process affected the archtitecture of the electrospun scaffold. Tensile testing was used to ascertain mechanical properties (strength, modulus, failure stress, ductility) of both unmodified and reinforced electrospun scaffolds. An in vivo bone graft model was used to assess biocompatibility. Specifically, reinforced scaffolds were used as a membrane cover for bone graft particles implanted into rat calvarial defects, and implant sites were examined histologically. Results We determined that the tensile strength and elastic modulus were markedly increased, and ductility reduced, by the addition of the PLA meshes to the electrospun scaffolds. Furthermore, the scaffolds maintained their matrix-like structure after being reinforced with the 3D printed PLA. There was no indication at the graft/tissue interface that the reinforced electrospun scaffolds elicited an immune or foreign body response upon implantation into rat cranial defects. Conclusion 3D-printed mesh reinforcements offer a new tool for enhancing the mechanical strength of electrospun scaffolds while preserving the advantageous extracellular matrix-like architecture. The modification of electrospun scaffolds with 3D-printed reinforcements is expected to expand the range of clinical applications for which electrospun materials may be suitable.