AbstractTranscranial direct current stimulation (TDCS) has been widely used to improve cognitive function. However, current deficiencies in mechanistic understanding hinders wider applicability. To clarify its physiological effects, we acquired fMRI whilst simultaneously acquiring TDCS to the right inferior frontal gyrus (rIFG) of healthy human participants, a region involved in coordinating activity within brain networks. TDCS caused widespread modulation of network activity depending on brain state (‘rest’ or choice reaction time task) and polarity (anodal or cathodal). During task, TDCS increased salience network activation and default mode network deactivation, but had the opposite effect during ‘rest’. Furthermore, there was an interaction between brain state and TDCS polarity, with cathodal effects more pronounced during task performance and anodal effects more pronounced during ‘rest’. Overall, we show that rIFG TDCS produces brain state and polarity dependent effects within large-scale cognitive networks, in a manner that goes beyond predictions from the current literature.