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Osteoid osteoma is one of the most frequent benign musculoskeletal neoplasm. Radiofrequency ablation is the method of choice for non-conservative treatment of osteoid osteoma. Recently, high-intensity focused ultrasound (HIFU) has been proposed as a safer option. The objective of this study is to review the efficacy and side effects of HIFU in the management of osteoid osteoma. A comprehensive search was conducted in PubMed, Science Direct, and Clinical Key until June 30, 2022. Demographic data, baseline characteristics, success rates, pre- and post-procedure pain scores, recurrences, and complications were recorded. Eleven studies were included in this systematic review. Pooled analysis that involved 186 subjects resulted in an overall success rate of 91.94%. Recurrence was reported in two studies, in which it occurred in 4/177 (2.26%) subjects. Skin burn was found in 1 (0.54%) patients. No major or other complications were reported. Three studies compared the success rate of HIFU and RFA. Success rate was slightly higher in the RFA group with insignificant difference (p = 0.15). High-intensity focused ultrasound showed promising results. It offers a safer treatment approach for osteoid osteoma, especially in children, and can be considered for recalcitrant cases after RFA. Nonetheless, more studies are expected in the future., (© 2023. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)