Background: High-definition transcranial direct current stimulation (HD-tDCS) may allow more specific neural modulation than conventional-tDCS., Objective: We compared safety, tolerability, blinding efficacy and cognitive effects of a novel HD-tDCS set-up to that of conventional-tDCS and established compatibility with simultaneous functional magnetic resonance imaging (fMRI)., Methods: Two groups of healthy participants completed a visual flanker task either with conventional (N = 30) or HD-tDCS (N = 30) administered to the right dorsolateral prefrontal cortex (1 mA) in a double-blind, sham-tDCS-controlled, cross-over design. HD-tDCS was administered with a one-channel DC-stimulator using a small conductive rubber "centre" electrode and a circular return electrode, mimicking the frequently used 4 × 1 HD-tDCS set-up. Tolerability, adverse effects, impact on performance and blinding efficacy were compared within and between the two montages. In a separate experiment, potential heating and impact on image quality of the novel HD-tDCS set-up were assessed during simultaneous fMRI., Results: Both montages elicited only mild adverse effects and those were less pronounced for the novel HD-tDCS set-up. Participant and investigator blinding was achieved with both montages. Only HD-tDCS resulted in significant modulation of the conflict adaptation effect during the flanker task; however, no differences were found for the direct comparison of the two montages. No significant heating occurred during fMRI and only minor effects on image quality were observed during HD-tDCS., Conclusions: This study confirmed safety, tolerability and blinding efficacy of a novel, re-usable and MRI-compatible HD-tDCS set-up. It also highlights its potential to exert beneficial effects on behavioural performance. Use of this novel set-up during simultaneous fMRI in future studies will help clarify the neural mechanisms by which this HD-tDCS impacts on behavioural and neural function., (Copyright © 2016 Elsevier Inc. All rights reserved.)