Plasma treatment of electrospun poly(c-caprolactone) (PCL) nanofiber random mats and aligned meshes is studied. The changes in the surface chemistry, and mechanical and biological properties of the PCL nanofibers induced by NH3 + O-2 plasma treatment are evaluated using surface contact angle measurements, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), tensile tests, and cell culture. It was found that plasma treatment resulted in a significant increase in surface hydrophilicity of the PCL nanofibers, with the water contact angle reduced from similar to 135 degrees to 0 degrees. XPS surface characterization indicates that the plasma treatment introduced new functional and polar groups on the fiber surface. Tensile test results show that, after the plasma treatment, the ultimate tensile strength and the ultimate strain of both the PCL nanofiber random mats and aligned meshes were reduced. The phenomenon indicates that the plasma etching effect occurred on the PCL nanofiber surfaces. When cultured with mouse osteoblast cells (MC3T3-E1), the plasma-treated PCL nanofiber random mats and aligned meshes yielded much higher cell proliferation rates compared to those obtained for the untreated controls. Environmental SEM examination shows that the plasma treatment significantly enhanced cell growth along the aligned PCL nanofibers. These results indicate that plasma surface modification of electrospun nanofibers has great potential in the development of novel polymeric scaffolds for tissue engineering applications, such as bone healing and cartilage repair.