Purpose: We investigated the risk factors influencing MR changes associated with sacral injury from ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. Methods: We retrospectively analyzed a total of 346 patients with symptomatic uterine fibroids who received USgHIFU ablation. All of the patients underwent contrast-enhanced magnetic resonance imaging (CE-MRI) before and after treatment. Injury to the sacrum was set as the dependent variable, while fibroid features and the treatment parameters were set as independent variables. These variables were used to assess respectively their correlation with sacral injury by using univariate and multivariate analyses. Results: The results of univariate analysis revealed that the volume, distance from the fibroid to the skin, maximal diameter, distance from the fibroid to the sacrum, fibroid types, degree of enhancement, therapeutic dosimetry (TD), energy efficiency factor (EEF) and non-perfused volume (NPV) ratio manifested significant correlations with the sacral injury (p < .05). Multivariate analysis showed that the degree of enhancement, TD and EEF were independent risk factors for sacral injury (p < .05), while the distance from fibroid to sacrum and intramural or subserosal types were protective factors (p < .05). The incidence of sacral tail pain and leg pain showed a significant positive correlation with sacral injury (p < .05). Conclusion: As important affecting factors, the degree of enhancement, distance from fibroid to sacrum and fibroid types all possess significant correlations with MR changes associated with sacral injury.