The aim of this study was to evaluate the long-term efficacy of a single ultrasound-guided high-intensity focused ultrasound (US-HIFU) treatment in patients with breast fibroadenoma (FA) in terms of volume and pain reduction as well as palpation findings. From december 2013 until november 2014 27 women with a symptomatic FA were treated in one HIFU-session. Follow-up visits were performed after 7 days, 6 months and 1, 2, 3 and 5 years with clinical examination and ultrasound. One year after the procedure, a core needle biopsy of the residual lesion was offered. There was a significant volume reduction 6 months after HIFU from 1083.10 to 347.13 mm3 (p < 0.0001) with a mean volume reduction ratio (VRR) of 61.63%. Thereafter the FAs showed a further, but no longer significant decrease in size. One patient with an initial incomplete ablation and histologically confirmed persistent vital cells after 1 year showed a strong regrowth after 3 years. Excluding this patient from analysis, the mean VRR at months 12, 24, 36, and 60 was 86.44%, 94.44%, 94.90%, and 97.85%, respectively. Before HIFU, 59.26% of the patients had pain (22.33/100 VAS) which decreased to 6.56/100 after 12 months and remained reduced over the 5 year follow up period. A decrease in palpability from 85.19 to 7.69% was observed within 24 months. A single HIFU intervention let to a substantial reduction in size, pain, and palpability with its most potential effect during the first 12 months. Subsequently, the observed effect remained stable over a 5 year follow up period. Incomplete initial treatment was associated with the risk of regrowth.