Purpose <p>Patients with localized prostate cancer have various treatment options. Decision regret from a patient’s view is an unpleasant feeling concerning a decision in health care. We aimed to explore regret and its determinants after external beam radiotherapy (EBRT) with a high dose-rate brachytherapy (HDR-BT) boost as traditional method of treatment intensification.</p> Methods <p>We conducted a secondary analysis of a cross-sectional study. Patients were enrolled at least two years after EBRT + HDR-BT. Decision regret was measured using the Decision Regret Scale (0–100). Covariables included patient characteristics, dose to organs at risk and patient-reported outcomes (PRO) including EPIC- 26, EORTC QLQ-C30, and PSCC. We used Pearson’s correlation and one-way ANOVA analyses.</p> Results <p>Among 108 patients, the median age was 73 and the median interval since treatment was 4&#xa0;years. The mean score of decision regret was 11 (SD: 14). No (0), mild (1–25), or strong (&gt; 25) decision regret was present in 49% (53/108), 39% (42/108), and 12% (13/108) of the patients, respectively. PRO were associated with stronger decision regret including worse urinary incontinence (r = − 0.198; p = 0.046), worse urinary irritative/obstructive symptoms (r = − 0.203; p = 0.045), worse bowel function (r = − 0.312; p = 0.001), worse hormonal function (r = − 0.289; p = 0.003), lower levels of shared-decision making (r = − 0.292; p = 0.002), and lower patient satisfaction (r = − 0.326; p &lt; 0.001).</p> Conclusion <p>Long-term decision regret is mild among patients with prostate cancer treated with EBRT + HDR-BT. PRO were associated with decision regret which should be respected in clinical practice.</p> Trial registration <p>The study protocol was registered prior to patient accrual on the Open Science Framework (doi.org/10.17605/OSF.IO/A6DC3).</p>