Electrospun scaffolds play important roles in the fields of regenerative medicine and vascular tissue engineering. The aim of the research described here was to develop a vascular scaffold that mimics the structural and functional properties of natural vascular scaffolding. The mechanical properties of artificial vascular tissue represent a key issue for successful transplantation in small diameter engineering blood vessels. We blended silk fibroin (SF) and fibrin to fabricate a composite scaffold using electrospinning to overcome the shortcomings of fibrin with respect to its mechanical properties. Subsequently, we then carefully investigated the morphological, mechanical properties, hydrophilicity, hemocompatibility, degradation, cytocompatibility and biocompatibility of the SF/fibrin (0:100), SF/fibrin (15:85), SF/fibrin (25:75), and SF/fibrin (35:65) scaffolds. Based on these in vitro results, we implanted SF/fibrin (25:75) vascular scaffold subcutaneously and analyzed its in vivo degradation and histocompatibility. The fiber structure of the SF/fibrin hybrid scaffold was smooth and uniform, and its fiber diameters were relatively small. Compared with the fibrin scaffold, the SF/fibrin scaffold clearly displayed increased mechanical strength, but the hydrophilicity weakened correspondingly. All of the SF/fibrin scaffolds showed excellent blood compatibility and appropriate biodegradation rates. The SF/fibrin (25:75) scaffold increased the proliferation and adhesion of MSCs. The results of animal experiments confirmed that the degradation of the SF/fibrin (25:75) scaffold was faster than that of the SF scaffold and effectively promoted tissue regeneration and cell infiltration. All in all, the SF/fibrin (25:75) electrospun scaffold displayed balanced and controllable biomechanical properties, degradability, and good cell compatibility. Thus, this scaffold proved to be an ideal candidate material for artificial blood vessels.© 2024. The Author(s).