Safe and long-term electrical stimulation of neurons requires charge injection without damaging the electrode and tissue. A common strategy to diminish adverse effects includes the modification of electrodes with materials that increases the charge injection capacity. Due to its high capacitance, the conducting polymer PEDOT:PSS is a promising coating material; however, the neural stimulation performance in terms of stability and safety remains largely unexplored. Here, PEDOT:PSS-coated platinum (Pt-PEDOT:PSS) microelectrodes are examined for neural stimulation and compared to bare platinum (Pt) electrodes. Microelectrodes in a bipolar configuration are used to deliver current-controlled, biphasic pulses with charge densities ranging from 64 to 255 μC cm−2. Stimulation for 2 h deteriorates bare Pt electrodes through corrosion, whereas the PEDOT:PSS coating prevents dissolution of Pt and shows no degradation. Acute stimulation of primary cortical cells cultured as neurospheres shows similar dependency on charge density for Pt and Pt-PEDOT:PSS electrodes with a threshold of 127 μC cm−2 and increased calcium response for higher charge densities. Continuous stimulation for 2 h results in higher levels of cell survival for Pt-PEDOT:PSS electrodes. Reduced cell survival on Pt electrodes is most profound for neurospheres in proximity of the electrodes. Extending the stimulation duration to 6 h increases cell death for both types of electrodes; however, neurospheres on Pt-PEDOT:PSS devices still show significant viability whereas stimulation is fatal for nearly all cells close to the Pt electrodes. This work demonstrates the protective properties of PEDOT:PSS that can be used as a promising approach to extend electrode lifetime and reduce cell damage for safe and long-term neural stimulation.