DTI is sensitive to tract-specific FA changes and thereby can be used to inform on therapeutic mechanisms and optimal targeting strategies for MRI-guided high intensity–focused ultrasound. Here, we used probablilistic tractography to investigate white matter fibre tract changes in essential tremor patients treated with MRIgHIFU. On the treated side, a significant decrease in FA was detected in the tracts projecting between the thalamus and motor cortex and between the dentate nucleus and the thalamus (i.e. the dentato-rubro-thalamic tract). These decreases in FA were correlated with the degree of tract-lesion overlap. Additionally, the post-treatment FA decrease in the tracts projecting between the thalamus and the motor cortex were positively correlated with clinical improvement. Interestingly, tract changes were also observed in the medial lemniscus of the contralesional side, possibly indicating global changes in brain connectivity.