A cochlear implant is a surgically implanted device that helps to restore hearing for most severe hearing impaired patients. During the first 2–3 weeks after implantation of a cochlear implant electrode array, the electrical impedance at the electrode contacts increases. This increase is typically explained by the formation of fibrous tissue around the electrode array. To improve the electrode nerve interface in these patients, it is aimed at a reduction of tissue formation around the electrode array after implantation. Previously we have demonstrated that nanostructuring of platinum surfaces can inhibit fibroblast growth in vitro. In the current study we generated nanostructures directly on the surfaces of cochlear implant electrodes and tested their potential to reduce connective tissue formation around the electrode array in vivo by means of electrophysiological measurements. Guinea pigs were implanted with unstructured control or surface structured electrode arrays for 4 weeks. Impedance measurements were performed during the first 2 weeks daily, later weekly. Recorded impedances were typically lower for surface functionalized electrodes. Nanostructuring of the surface of the stimulating contacts of CI electrodes additionally resulted in a delayed increase in impedance showing that this modification has the potential for in vivo applications.