ObjectiveTo assess the oncological and functional outcomes of focal high‐intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3‐year prospective study was undertaken using periodic post‐ablation saturation biopsies.Patients and MethodsMen with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate‐specific antigen (PSA) level of ≤15 ng/mL, clinical T1c‐T2, and a life expectancy of ≥10 years. The primary endpoint was failure‐free survival (FFS), defined as absence of clinically significant PCa (csPCa) in‐ or out‐of‐field on protocol‐mandated saturation biopsy, no whole‐gland or systemic salvage treatment, PCa metastasis, or PCa‐related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient‐reported outcome measures addressing urinary, sexual, and bowel function.ResultsA total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow‐up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80–88%), 57% (95% CI 48–69%) and 44% (95% CI 34–56%), respectively. Using the second definition, FFS were 88% (95% CI 81–95%), 70% (95% CI 61–81%) and 65% (95% CI 55–77%), respectively. The 3‐year cancer‐specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84–93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed.ConclusionsFocal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer‐free after 3 years. Whole‐gland treatment was avoided in 81%. Early follow‐up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.