BACKGROUND: Bilateral deep brain stimulation (DBS) and unilateral magnetic resonance-guided focused ultrasound (MRgFUS), with potential future second-side treatment targeting the thalamic ventral intermediate nucleus (VIM), are currently the two best-established interventions for pharmaco-resistant tremors, but treatment selection is hampered by the lack of comparative evidence. OBJECTIVE: To provide the first direct within-center and within-surgeon comparison between bilateral VIM-DBS and unilateral VIM-MRgFUS, applying consistently timed and elaborated efficacy and safety assessements. METHODS: In this retrospective study, we included patients having received bilateral VIM-DBS (n = 30) or unilateral VIM-MRgFUS (n = 52) performed by one single neurosurgeon between 2014 and 2022. Efficacy was primarily measured by the improvement of the Washington Heights-Inwood Genetic Study of Essential Tremor scale in the more affected hand at 6 months. Regarding safety, we compared treatment-, procedure-, and hardware-related adverse events (AEs), graded by impact on activities of daily living (ADLs), and serious AEs (SAEs), retrospectively defined based on prolonged/repeated hospitalizations or persistent symptoms affecting ADLs. RESULTS: We found equivalent tremor reduction in the more affected hand (DBS: 62.4% [41.3-87.9] vs. MRgFUS: 69.4% [42.4-77.7]
P = 0.958), but contralateral and axial tremors improved only with bilateral DBS. DBS was associated with a higher rate of procedure- and hardware-related AEs (17% vs. 2%
P = 0.023) but a nonsignificantly lower rate of persistent treatment-related AEs affecting ADLs at 6 months (7% vs. 13%
P = 0.343). Overall, the rates of SAEs (23.3% vs. 19.2%
P = 0.779) and persistent deficits affecting ADLs at 6 months (10% vs. 13%
P = 0.82) were similar. CONCLUSIONS: Despite distinct safety profiles, both interventions produced a similar burden of AEs. Tremor control was equivalent on the more affected side, whereas contralateral and axial tremors improved only after bilateral DBS. © 2025 International Parkinson and Movement Disorder Society.