Abbreviations & AcronymsObjectives: To evaluate the impact of transurethral resection of the prostate on quality of life after radiotherapy for prostate cancer. Methods: A group of 49 consecutive patients with and 487 without prior transurethral resection of the prostate responded to the Expanded Prostate Cancer Index Composite questionnaire before, on the last day, and a median time of 2 months and 16 months after external beam radiotherapy (70-78 Gy). A matched-pair analysis was used to avoid the influence of treatment-associated confounding factors, including dose, treatment volume and hormonal therapy. Results: Significantly smaller acute urinary score changes relative to baseline levels resulted with versus without prior transurethral resection of the prostate (mean function/ bother score decrease of 3/6 vs 18/21 points at the end of radiotherapy; P < 0.01), affecting urinary incontinence (pads to control urinary leakage in 4% vs 24%; P = 0.03) and irritative/ obstructive symptoms (big/moderate problem with weak urinary stream in 11% vs 37%; P = 0.02). As opposed to acute changes, transurethral resection of the prostate was a significant predisposing factor for a long-term urinary function score decrease >10 points (20% vs 6% of patients with vs without prior resection; P = 0.04). Urinary incontinence risk was higher for patients with a longer time from resection to radiotherapy. Conclusions: Transurethral resection of the prostate significantly affects acute (considerably fewer symptoms) and long-term (relevant toxicity in some cases) urinary quality of life after radiotherapy for prostate cancer.