A biomimetic vascular scaffold with excellent mechanical properties and biocompatibility is urgently needed, and designing such a scaffold is a challenge. The majority of vascular scaffolds have satisfactory biocompatibility, but poor mechanical properties. Herein, biodegradable poly(l-lactide-co-caprolactone) (PLCL) with biomimetic mechanical properties was used to prepare small-diameter (< 1.5 mm) PLCL/tussah silk fibroin (TSF) nanofiber vascular scaffolds grafted with TSF using the core-spun electrospinning technology. The morphology, biocompatibility, and mechanical properties of the PLCL/TSF nanofiber vascular scaffolds were characterized. The diameter of PLCL/TSF nanofibers was almost unchanged after grafting TSF with an average diameter of 408 +/- 13 nm and a reduced water contact angle of 56 +/- 8 degrees. The protein adsorption was twice that of pure PLCL nanofiber vascular scaffolds. Remarkably, PLCL/TSF nanofiber vascular scaffolds displayed excellent mechanical properties. Their radial tensile strength and axial Young's modulus were twice and more than three times those of traditional nanofiber vascular scaffolds, respectively. The biological properties of PLCL/TSF nanofiber vascular scaffolds were evaluated by in vitro culture of vascular endothelial cells. The scaffolds effectively promoted vascular endothelial cell adhesion and proliferation. The developed PLCL/TSF nanofiber vascular scaffolds are potentially valuable for use as readily available vascular grafts.