Biofilms are a common cause of persistent infections on medical devices as they are easy to form and hard to treat. The objective of this study was for the first time to coat selenium (a natural element in the body) nanoparticles on the surface of polycarbonate medical devices (such as those used for medical catheters) and to examine their effectiveness at preventing biofilm formation. The size and distribution of selenium coatings were characterized using scanning electron microscopy and atomic force microscopy. The strength of the selenium coating on polycarbonate was assessed by tape-adhesion tests followed by atomic absorption spectroscopy. Results showed that selenium nanoparticles had a diameter of 50–100 nm and were well distributed on the polycarbonate surface. In addition, more than 50% of the selenium coating survived the tape-adhesion test as larger nanoparticles had less adhesion strength to the underlying polycarbonate substrate than smaller selenium nanoparticles. Most significantly, the results of this in vitro study showed that the selenium coatings on polycarbonate significantly inhibited Staphylococcus aureus growth to 8.9% and 27% when compared with an uncoated polycarbonate surface after 24 and 72 h, respectively. Importantly, this was accomplished without using antibiotics but rather with an element (selenium) that is natural to the human body. Thus, this study suggests that coating polymers (particularly, polycarbonate) with nanostructured selenium is a fast and effective way to reduce bacteria functions that lead to medical device infections. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 3205–3210, 2012.