OBJECTIVES: To assess change in functional outcomes after second focal-HIFU compared to one focal-HIFU treatment. PATIENTS AND METHODS: In this multi-centre study (2005-2016), 821 men underwent focal-HIFU for localised non-metastatic prostate cancer. PROMS on IPSS, pad usage and erectile function (EF-score) were prospectively collected for up to 3 years. Inclusion criteria were men who had completed at least one follow-up questionnaire. The primary outcome was comparison of change in functional outcomes between baseline and follow-up after one focal-HIFU or second focal-HIFU using IPSS, EPIC and IIEF questionnaires. RESULTS: Of 821 men, 654 had one focal-HIFU and 167 had a second focal-HIFU. 355 (54.3%) men undergoing one focal-HIFU and 65 (38.9%) having second focal-HIFU returned follow-up questionnaires, respectively. Mean age and PSA were 66.4 and 65.6 years, and 7.9 and 8.4 ng/ml respectively. After one focal-HIFU, mean change in IPSS was -0.03 (p=0.02) and IIEF (EF-score) -0.4 (p=0.02) at 1-2 years with no subsequent decline. Absolute rates of erectile dysfunction increased from 9.9% to 20.8% (p=0.08), leak-free continence decreased from 77.9% to 72.8% (p=0.06) and pad-free continence from 98.6% to 94.8% (p= 0.07) at 1-2 years, respectively. IPSS prior to second focal-HIFU compared to baseline IPSS prior to first focal-HIFU was lower by -1.3 (p=0.02), but mean IPSS change was +1.4 at 1-2 years (p=0.03) and +1.2 at 2-3 years (p=0.003) after second focal-HIFU. Mean change in EF-score after second focal-HIFU was -0.2 at 1-2 years(p=0.60) and -0.5 at 2-3 years(p=0.10) with 17.8% and 6.2% new erectile dysfunction. New pad use was 1.8% at 1-2 years and 2.6% at 2-3 years. CONCLUSION: A second focal-HIFU procedure causes minor detrimental effects in urinary and erectile function. Data can be used to counsel patients with non-metastatic prostate cancer prior to considering HIFU therapy.