Radial metallic nanopillar/nanowire structures can be created by a controlled radiofrequency (RF) plasma processing technique on the surface of certain alloy wires, including important biomedical alloys such as MP35N (Co–Ni–Cr–Mo alloy), platinum–iridium and stainless steel. In electrode applications such as pacemakers or neural stimulators, the increase in surface area in elongated MP35N nanopillars allows for decreased surface impedance and greater current density. However, the nanopillar height on MP35N alloy tends to be self-limiting at ∼1–3μm. The objective of this study was to further elongate the radial nanopillars so as to reduce electrode impedance for biomedical electrode applications. Intelligent experimental design allowed for efficient investigation of processing parameters, including plasma material, process duration, power, pressure and repetition. It was found that multi-step repeated processing in the parameter-controlled RF environment could increase nanopillar height to ∼10μm, a 400% improvement, while the RF plasma processing with identical total duration but in a single step did not lead to desired nanopillar elongation. Measurement of electrode impedance in phosphate-buffered saline solution showed an associated decrease to one-fifth of the surface impedance of unprocessed wire for signals below 100Hz. For the purposes of this study, MP35N and Pt–Ir wires were characterized and demonstrated augmented surface impedance properties which, in combination with superior cell integration, enhanced biomedical electrode performance.