Ideal synthetic polymeric vascular scaffolds should provide an excellent physiological environment to facilitate cell adhesion and growth, and appropriate physicochemical properties to prevent thrombogenicity and secondary infection. In the current study, a multifunctional polycaprolactone (PCL) surface for simultaneously enhancing the adhesion and proliferation of endothelial cells (ECs), as well as inhibiting pathogenic microbial adhesion and preserving hemocompatibility was demonstrated. The achievement of such a multifunctional surface was accomplished by the conjugation of Arg-Glu-Asp-Val (REDV) short peptides to zwitterionic polycarboxybetaine brush-grafted PCL films via surface-initiated atom transfer radical polymerization (ATRP). An in vitro antibacterial test demonstrated a high antibacterial efficiency against Gram-negative E. coli on the as-synthesized REDV-conjugated zwitterionic polycarboxybetaine hybrid surfaces. In addition, the platelet adhesion assay results showed that the zwitterionic polycarboxybetaine-REDV conjugates led to the amelioration of surface hemocompatibility, and this enhancement was not negated by the conjugation of REDV. Celluar studies further revealed that the EC attachment and proliferation were substantially improved by zwitterionic polycarboxybetaine-REDV conjugation as compared to other PCL surfaces. The current multifunctional PCL hybrid surface is potentially useful in tissue engineered constructs for vascular graft applications as it allows for better initial attachment and proliferation of ECs and improved hemocompatibility, whilst simultaneously reducing graft-associated infections.