Blending two polymers is a common and effective way to develop a new material with combinations of properties not possessed by individual polymers and to overcome some limitations of individual components. This study aimed at developing a novel scaffold to mimic natural extracellular matrix (ECM) and to promote blood compatibility. Heparin (Hep) and bacterial cellulose (BC), for the first time, were hybridized to prepare a novel class of nanofibrous scaffold for vascular tissue engineering by the co-synthesis process. The morphology of Hep–BC hybrid nanofiber was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The hybrid was further characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The results show that hybridizing heparin brings anticoagulant sulfate groups into BC nanofiber and that Hep–BC nanofiber has a different structure in comparison to pristine BC. This work paves a new way of improving anticoagulant property of tissue engineered vessels other than coating process. Copyright © 2010 John Wiley & Sons, Ltd.