OBJECTIVES: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a novel, minimally invasive ablative treatment for essential tremor (ET). The use of a four-tract probabilistic tractography technique, targeting the intersection between the dentato-rubro-thalamic tracts (both decussating and non-decussating), while evaluating the corticospinal tract and the medial lemniscus, may obtain immediate clinical results with reduced adverse events. Our aim is to present our experience with the four-tract technique for patients undergoing ET treatment with MRgFUS. METHODS: Retrospective analysis of a prospective database of consecutive patients undergoing ET treatment in a single center from February 2022 to February 2023. Procedural parameters were collected, and tremor improvement was assessed with the Clinical Rating Scale for Tremor (CRST) at baseline and at 3 and 6 months. Adverse events were also reported. RESULTS: Forty-three patients (median age, 72 years [interquartile range, 66-76]; 22 females) were evaluated. Tremor improved significatively in all CRST subsections at 3 months, including the CRST part A + B treated hand tremor (22 [19-27] vs 4 [2-7], p < 0.001) and CRST part C (16 [13-19] vs 3 [1-4], p < 0.001). Differences persisted significant at 6 months. Adverse events were few (4.1% of paresthesias and 12.5% of objective gait disturbance at follow-up) and recorded as mild. The median number of sonications was 7 [6-8] and mean operative time 68.7 ± 24.2 min. CONCLUSION: Our data show support for the feasibility and benefits of systematic targeting approach with four-tract probabilistic tractography for treating ET using MRgFUS. CLINICAL RELEVANCE STATEMENT: An approach with four-tract probabilistic tractography for treating essential tremor (ET) patients with magnetic resonance-guided focused ultrasound decreases interindividual variability with good clinical outcomes, low number of sonications, few adverse effects, and short procedure times. KEY POINTS: • The optimal target for the treatment of essential tremor with MR-guided focused ultrasound remains unknown. • Four-tract probabilistic tractography is a feasible technique that reduces interindividual variability, with good clinical results, few side effects, and short operative time. • The four-tract tractography approach can be performed using different MRI scanners and post-processing software in comparison with the initial description of the technique.