OBJECTIVE: To evaluate the middle-term efficacy and complications of ultrasound-guided high intensity focused ultrasound (USgHIFU) for the treatment of symptomatic uterine fibroids in an NHS population. METHODS: A prospective observational single-center study at a single university hospital in Oxford, UK. Patients with symptomatic uterine fibroids who declined standard surgical/radiological intervention and were referred to the HIFU unit were considered for USgHIFU treatment. Clinical evaluation, adverse event monitoring, uterine fibroid symptoms and health-related quality of life questionnaire (UFS-QOL) and contrast-enhanced pelvic magnetic resonance imaging (MRI) were performed before and at regular intervals after treatment to assess patient outcome. RESULTS: 12 of 22 referred patients underwent one session of USgHIFU ablation of 14 fibroids overall and received a two-year follow-up. No serious adverse events were reported, but a second-degree skin burn was observed in one patient who had a surgical scar from a previous caesarean section. Mean symptom severity scores (SSS-QOL) improved significantly from 56.5 ± 29.1 (SD) at baseline to 33.4 ± 23.3 (p < 0.01) at three months, 45.0 ± 35.4 (p < 0.05) at one year and 40.6 ± 32.7 (p < 0.01) at two years post-treatment. The mean non-perfused volume ratio was 67.7 ± 39.0 % (SD) in the treated fibroids (n = 14) within three months of treatment. The mean volume reduction rates of the treated fibroids were 23.3 ± 25.5 % (SD) at 3 months post-treatment (p < 0.01, n = 14), 49.3 ± 23.7 % at 12 months (p < 0.05, n = 8), and 51.9 ± 11.1 % at 24 months (p < 0.005, n = 8). CONCLUSION: This study demonstrates the clinical efficacy of USgHIFU ablation of uterine fibroids and the low risk of complications. We believe that this noninvasive approach may offer an alternative therapy for women with symptomatic uterine fibroids. While HIFU is fast becoming the standard of care for fibroid ablation in other countries, to our knowledge, this study is the first to present clinical experience of US-guided HIFU ablation of symptomatic uterine fibroids in an NHS population. PLAIN LANGUAGE SUMMARY: High intensity focused ultrasound (HIFU) can be used for the noninvasive ablation of symptomatic uterine fibroids, and MR-guided treatment has already gained FDA approval. Ultrasound-guided HIFU has the advantage of offering practicalities in anesthesia and considerable cost-savings over MR-guided treatments. In this prospective study we have demonstrated the middle-term efficacy and favorable safety profile of ultrasound-guided HIFU for the treatment of symptomatic uterine fibroids for the first time in an NHS population.