BackgroundMagnetic resonance–guided focused ultrasound (MRgFUS) for treatment of essential tremor (ET) traditionally targets the ventral intermediate (Vim) nucleus. Recent strategies include a secondary lesion to the posterior subthalamic area (PSA).ObjectiveThe aim was to compare lesion characteristics, tremor improvement, and adverse events (AE) between patients in whom satisfactory tremor suppression was achieved with lesioning of the Vim alone and patients who required additional lesioning of the PSA.MethodsRetrospective analysis of data collected from ET patients treated with MRgFUS at St Vincent's Hospital Sydney was performed. Clinical Rating Scale for Tremor (CRST), hand tremor score (HTS), and Quality of Life in Essential Tremor Questionnaire (QUEST) were collected pre‐ and posttreatment in addition to the prevalence of AEs. The lesion coordinates and overlap with the dentatorubrothalamic tract (DRTT) were evaluated using magnetic resonance imaging.ResultsTwenty‐one patients were treated in Vim only, and 14 were treated with dual Vim–PSA lesions. Clinical data were available for 29 of the 35 patients (19 single target and 10 dual target). At follow‐up (mean: 18.80 months) HTS, CRST, and QUEST in single‐target patients improved by 57.97% (P < 0.001), 36.71% (P < 0.001), and 58.26% (P < 0.001), whereas dual‐target patients improved by 68.34% (P < 0.001), 35.37% (P < 0.003), and 46.97% (P < 0.005), respectively. The Vim lesion of dual‐target patients was further anterior relative to the posterior commissure (PC) (7.84 mm), compared with single‐target patients (6.92 mm), with less DRTT involvement (14.85% vs. 23.21%). Dual‐target patients exhibited a greater proportion of patients with acute motor AEs (100% vs. 58%); however, motor AE prevalence was similar in both groups at long‐term follow‐up (33% vs. 38%).ConclusionPosterior placement of lesions targeting the Vim may confer greater tremor suppression. The addition of a PSA lesion, in patients with inadequate tremor control despite Vim lesioning, had a trend toward better long‐term tremor suppression; however, this approach was associated with greater prevalence of gait disturbance in the short term.