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RATIONALE AND OBJECTIVES We aimed to investigate the role of magnetic resonance imaging parameters in predicting the treatment outcome of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids with a nonperfused volume (NPV) ratio of at least 90%. MATERIAL AND METHODS A total of 120 women who underwent HIFU treatment were divided into groups 1 (n = 72) and 2 (n = 48), comprising patients with an NPV ratio of at least 90% and less than 90%, respectively. Multivariate logistic regression analyses were carried out to investigate the potential predictors of the NPV ratio of at least 90%. The NPV ratios immediately post-treatment, therapeutic efficacy at 6 months' follow-up, and safety in terms of adverse effects and changes in anti-Mullerian hormone level were assessed. RESULTS By introducing multiple predictors obtained from multivariate analyses into a generalized estimating equation model, the results showed that the thickness of the subcutaneous fat layer in the anterior abdominal wall, peak enhancement of fibroid, time to peak of fibroid, and the ratio of area under the curve of fibroid to myometrium were statistically significant, except T2 signal intensity ratio of fibroid to myometrium, hence predicting an NPV ratio of at least 90%. No serious adverse effects and no significant difference between the anti-Mullerian hormone levels before or 6 months post-treatment were reported. CONCLUSIONS The findings in this study suggest that the achievement of NPV ratio of at least 90% in magnetic resonance imaging-guided HIFU treatment of uterine fibroids based on prediction model appears clinically possible without compromising the safety of patients.