The aim of the present study was to investigate factors affecting ablation effect and safety of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids (UFs).A retrospective analysis of 346 patients with symptomatic UFs who were treated with USgHIFU was performed. All UFs was grouped based on magnetic resonance imaging (MRI) characteristics before HIFU; all adverse events and treatment data were recorded during and after HIFU. One-way analysis of variance and multiple linear regression analysis were used to evaluate the effect of USgHIFU treatment and affecting factors.The results showed that the mean age of patients was 38.36.1 years, with the mean nonperfusion volume rate of 74.4 +/- 14.7% and the mean energy efficiency factor (EEF) of 7.2 +/- 4.8J/mm(3). Except for the size group, the ablation rate was significantly different (P<.001); and the anterior, intramural, hypointense (T2WI), and mild enhancement (T1WI contrast enhancement) UFs had the highest ablation rate. The EEF of the anterior, intramural, hypointense (T2WI), mild enhancement (T1WI contrast enhancement), and >5cm UFs had minimum value, with a statistically significant difference (P<.01). According to multiple linear regression model, the distance from the UFs ventral side to the skin, enhancement type on T1WI, size of UFs, signal intensity on T2WI, location of UFs, type and volume of fibroids all had a line relationship with EEF, and the enhancement type on T1WI was the greatest factor affecting the ablation effect. Some patients (37.6%) had thermal injury of the sacrum on MRI, but no serious adverse events were observed.Our results suggest that USgHIFU can be safely used and have a promising prospect for treating UFs, even though its effect may be affected by anatomical features, tissue characteristics, and blood supply.