INTRODUCTION: Essential tremor (ET) is a progressive disorder characterized by altered network connectivity between the cerebellum, thalamus, and cortical regions. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) of the ventral intermediate nucleus (VIM) is an effective, minimally invasive treatment for ET. The impact of MRgFUS interventions on regional Gray Matter Volume (GMV) are as yet not well understood. METHODS: Forty-six patients with medication-resistant ET underwent unilateral VIM-MRgFUS. Voxel-based morphometry was applied to investigate GMV changes over a time span of 6 months in the whole brain and the thalamus in particular to investigate local and distant effects. RESULTS: Clinically, contralateral tremor significantly decreased by 68 % at 6 months following MRgFUS. In addition to local GMV decreases in thalamic nuclei (VIM, ventral lateral posterior, centromedian thalamus and pulvinar), VBM revealed remote GMV decreases in the ipsilesional insula and the anterior cingulate cortex as well as the contralesional middle occipital gyrus. Increased GMV was found in the right superior and middle temporal gyrus, as well as in the left inferior temporal gyrus. There was no significant correlation between regional GMV declines and tremor improvement. However, temporal volume increases were associated with improved motor-related functional abilities and quality of life outcomes. CONCLUSION: Our findings implicate distributed structural changes following unilateral VIM-MRgFUS. Structural losses could reflect Wallerian degeneration of VIM output neurons or plasticity due to decreased sensory input following tremor improvement.