BACKGROUND AND PURPOSE: Little is known about the functional outcomes and health-related quality of life (HRQoL) following external beam radiation therapy (EBRT) combined with a high-dose rate brachytherapy boost (EBRT-BB) for the treatment of prostate cancer. We aimed to compare patient-reported outcomes of EBRT to those of EBRT-BB. METHODS AND MATERIALS: Patients diagnosed with intermediate-risk, high-risk or locally advanced prostate cancer (April 2014 to September 2016), who received EBRT in the English National Health Service within 18 months of diagnosis and responded to a national patient questionnaire, were identified from the National Prostate Cancer Audit. Adjusted linear regression was used to estimate differences in functional EPIC-26 domains and HRQoL (EQ-5D-5L) between treatment groups. Non-inferiority of EBRT-BB was determined if the lower 95% confidence limit did not exceed the established minimal clinically important difference (MCID). RESULTS: Of the 13,259 included men, 12,503 (94.3%) received EBRT and 756 (5.7%) received EBRT-BB. EBRT-BB was non-inferior compared to EBRT for the urinary incontinence, sexual, bowel and hormonal EPIC-26 domains. EBRT-BB resulted in significantly worse urinary irritation/obstruction scores than EBRT (-6.1; 95% CI: -8.8 to -3.4) but uncertainty remains as to whether this difference is clinically important (corresponding MCID of 5). CONCLUSIONS: There is no evidence to suggest that EBRT-BB results in any clinically important detriment in functional outcomes or HRQoL compared to men receiving EBRT only. Whilst statistically significantly worse urinary irritation/obstruction outcomes were reported in the EBRT-BB cohort, the threshold for a clinically significant difference was not exceeded and further research is required for confirmation.