In this article, the plasma surface modification effects on the chemical, mechanical, and biological properties of electrospun poly (ε-caprolactone) (PCL) random nanofiber meshes (NFMs) were investigated by adjusting plasma chemistry, that is, using glow discharges of N2+H2, NH3+O2, and Ar+O2 gas mixtures. The surface property changes of electrospun PCL NFMs after those plasma treatments were examined by water contact angle measurements and X-ray photoelectron spectroscopy. The experimental results showed that the plasma treatments introduced polar groups onto the surfaces and thus increased the surface hydrophilicity. From tensile test data, plasma treatment had limited effect on the mechanical properties of PCL random NFMs. The biological properties of the plasma-treated PCL NFMs were examined by cell proliferation assays using mouse osteoblast cells (MC3T3-E1). It was found that the plasma-treated PCL NFMs gave a higher proliferation rate and improved cell adhesion properties as compared with the untreated controls. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.