Electrospun nanofibers were widely studied to be applied as potential materials for tissue engineering. A new technology to make poly-L-lactic acid/chitosan core/shell nanofibers from heterologous solution by coaxial electrospinning technique was designed for vascular gasket. Chitosan surface was cross-linked by genipin and modified by heparin. Different ratios of PLA/CS in heterologous solution were studied to optimize the surface morphology of fibers. Clean core-shell structures formed with a PLA/CS ratio at 1:3. Superior biocompatibility and mechanical properties were obtained by optimizing the core-shell structure morphology and surface cross-linking of chitosan. UE7T-13 cells grew well on the core-shell structure fibers as indicated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) results and scanning electron microscopy (SEM) images. Compared with the pure PLA fiber meshes and commercial vascular patch, PLA/CS core-shell fibers had better mechanical strength. The elastic modulus was as high as 117.18 MPa, even though the yield stress of the fibers was lower than that of the commercial vascular patch. Attachment of red blood cell on the fibers was evaluated by blood anticoagulation experiments and in vitro blood flow experiments. The activated partial thromboplastin time (APTT) and prothrombin time (PT) value from PLA/CS nanofibers were significantly longer than that of pure PLA fibers. SEM images indicated there were hardly any red blood cells attached to the fibers with chitosan coating and heparin modification. This type of fiber mesh could potentially be used as vascular gasket.