Abstract Purpose Focal therapies (FTs) are investigated within prospective studies on selected patients treated for localized prostate cancer (PCa). Benefits are preservation of genitourinary function and reduced complications, but follow-up is elaborate and is associated with uncertainty as cancer-free survival appears to be lower compared to standard radical treatments. The aim of this study was to analyse patient-reported acceptance of FT and evaluate factors associated with treatment decision regret. Methods 52 patients who received focal high-intensity focused ultrasound for low- to intermediate-risk PCa between 2014 and 2019 within two prospective trials were eligible for a survey regarding PCa-related treatment regret and quality-of-life (Clark’s scale) and the following potential predictors: sociodemographic variables, Charlson Comorbidity Index, subjective aging (AARC-10 SF), and general health-related quality-of-life (SF-12). Cancer persistence/recurrence (multiparametric MRI and fusion biopsy after 12 months) and functional outcomes (EPIC-26 UI/UIO/S) data were also included in this study. Results The overall survey response rate was 92.3% (48/52 patients). Median follow-up was 38 months (interquartile range = 25–50 months). In total, ten patients (20.8%) reported treatment decision regret. In univariable analyses, a clinically meaningful increase in urinary incontinence showed a significant association (OR 4.43; 95% CI 0.99–20.53; p = 0.049) with regret. Cancer recurrence (OR 12.31; 95% CI 1.78–159.26; p = 0.023) and general health worry as a domain of Clark’s scale (OR 1.07; 95% CI 1.03–1.14; p < 0.01) were predictors of regret in a multivariable logistic regression model (AUC = 0.892). Conclusion Acceptance of FT is comparable to standard treatments. Extensive follow-up including regular PSA testing does not cause additional regret but careful patient selection and information before FT is crucial.