Abstract Background Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is effective in medication refractory essential tremor (ET). In recent years, evidence has accumulated that the region ventral to the VIM, the posterior subthalamic area (PSA), might be an equally or even more effective target for electrode implantation. However, this evidence is primarily based on case series, cross-sectional observations, and retrospective data. Methods/design A prospective crossover pilot study investigating the effects of PSA stimulation in medication refractory ET patients was designed. In this study, bilateral electrodes are implanted such that at least one of the electrode contacts is located in the PSA and VIM, respectively. This implantation approach allows (1) a prospective double-blind investigation of the effects of PSA stimulation compared to baseline, as well as (2) a crossover comparison between VIM and PSA stimulation with respect to tremor suppression and side effect profiles. Discussion The results of this double-blinded, prospective study will allow a better understanding of the effects and side effects of PSA compared to VIM-DBS in patients with ET. Trial registration German Clinical Trials Register: DRKS00004235 . Registered on 4 July 2012.