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MR-guided high-intensity focused ultrasound (MR-HIFU) is an effective method for treating symptomatic uterine fibroids, especially solitary lesions. The aim of our study was to compare the clinical and morphological outcomes of patients who underwent MR-HIFU due to solitary fibroid (SF) or multiple fibroids (MFs) in a prospective clinical trial. We prospectively included 21 consecutive patients with SF (10) and MF (11) eligible for MR-guided HIFU. The morphological data were assessed using mint Lesion™ for MRI. The clinical data were determined using the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire before and 6 months after treatment. Unpaired and paired Wilcoxon-test and t -tests were applied, and Pearson's coefficient was used for correlation analysis. A p -value of 0.05 was considered statistically significant. The volume of treated fibroids significantly decreased in both the SF (mean baseline: 118.6 cm 3 ; mean 6-month follow-up: 64.6 cm 3 ) and MF (107.2 cm 3 ; 55.1 cm 3 ) groups. The UFS-QOL showed clinical symptoms significantly improved for patients in both the SF and MF groups regarding concern, activities, energy/mood, and control. The short-term outcome for the treatment of symptomatic fibroids in myomatous uterus by MR-guided HIFU is clinically similar to that of solitary fibroids.