This study compares the stability of three variations of the conductive polymer poly(3,4-ethylenedioxythiophene) or PEDOT for neural micro-stimulation under both in vitro and in vivo conditions. We examined PEDOT films deposited with counter-ions tetrafluoroborate (TFB) and poly(styrenesulfonate) (PSS), andPSS combined with carbon nanotubes (CNTs).For the in vitro stability evaluation, implantable micro-wires were coated with the polymers, placed in a vial containing phosphate buffered saline (PBS) under accelerated aging conditions (60°C), and current pulses were applied. The resulting voltage profile was monitored over time. Following the same polymer deposition protocol, chronic neural micro-probes were modified and implanted in the motor cortex of two rats for the in vivo stability comparison. Similar stimulating current pulses were applied and the output voltage was examined. The electrochemical impedance spectroscopic (EIS) data were also recorded and fit to an equivalent circuit model that incorporates and quantifies the time-dependent polymer degradation and impedance associated with tissue surrounding each micro-electrode site.Both in vitro and in vivo voltage output profiles show relatively stable behavior for theTFB modified micro-electrodes compared to thePSS and CNT:PSS modified ones. EIS modeling demonstrates that the time-dependent increase in the polymeric resistance is roughly similar to the rise in the respective voltage output in vivo and indicates that the polymeric stability and conductivity, rather than the impedance due to the tissue response, is the primary factor determining the output voltage profile. It was also noted that the number of electrodes showing unit activity post-surgery did not decay forTFB as was the case forPSS and CNT:PSS.TFB may be an enabling material for achieving long lasting micro-stimulation and recording.