Objective: Holmes tremor (HT) is a complex syndrome characterized by resting, postural, and kinetic tremors. HT significantly impacts patients' quality of life (QOL) and daily activities. Conventional pharmacological treatments for HT often yield inconsistent results. Emerging surgical treatments such as deep brain stimulation and various thalamotomy techniques show promise but come with challenges, including adverse events (AEs) and potential tremor recurrence. This study aimed to evaluate the clinical outcomes of unilateral MRI-guided laser interstitial thermal therapy (MRIgLITT) thalamotomy in patients with medically intractable HT, focusing on tremor reduction, QOL, and AE incidence, and provide a comprehensive review of the literature on thalamotomy techniques for HT., Methods: Five patients with medically intractable HT underwent unilateral MRIgLITT thalamotomy between June 2020 and January 2023. Tremor severity was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) at baseline and at 3 and 12 months postoperatively. QOL was measured using the Quality of Life in Essential Tremor (QUEST) questionnaire and 39-item Parkinson's Disease Questionnaire (PDQ-39). Subjective patient-rated improvement was evaluated using the Patient Global Impression of Clinical Status (PGI-C) scale at 12 months. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE) before the procedure and at 12 months postoperatively. AEs were monitored throughout the follow-up period., Results: The mean patient age was 50.2 ± 22.37 years, with a mean tremor duration of 5.8 ± 4.55 years. Significant tremor reduction was observed in the treated hand, with mean TRS scores decreasing from 19.00 ± 4.36 at baseline to 11.20 ± 4.44 (p = 0.043) at 3 months and 13.40 ± 5.94 (p = 0.042) at 12 months, indicating a relative reduction of 41.05% and 29.47%, respectively. A significant effect was observed on the QUEST scale at 3 months (p = 0.043), but this effect was no longer present at 12 months. No significant effect was found on the PDQ-39 QOL scale. The PGI-C scale showed a high mean subjective improvement of 88.60% ± 8.36% at 12 months. One patient experienced severe AEs, including dysarthria, hemiparesis, and swallowing difficulties, which required prolonged hospitalization and multidisciplinary rehabilitation, but regressed within 3 months. Cognitive performance, as measured by the MMSE, remained stable (p = 0.785)., Conclusions: Unilateral MRIgLITT thalamotomy showed promise as a treatment for medically intractable HT, providing significant tremor reduction with a favorable safety profile. However, the potential for tremor recurrence and minimal functional improvement in fine motor skills highlight the need for long-term follow-up and further research. Larger, multicenter studies are necessary to validate these findings.