Background: Radiotherapy (RT) in combination with androgen deprivation therapy (ADT) for prostate cancer (PCa) carries a risk of gastrointestinal (GI) and genitourinary toxicity, which might affect the quality of life (QoL). The purpose of this study was to assess the QoL in patients with PCa before, during and after radiotherapy (RT) and to compare the QoL 1 year after RT to a normal population. Methods: The QoL was evaluated prospectively by the self-administered questionnaire SF-36 in 87 patients with PCa. The SF-36 was completed before RT (baseline), at start of RT, at end of RT and 1 year after RT. A mixed model analysis was used to determine the changes in QoL at each time point compared to baseline. The patients' QoL 1 year after RT was compared to a normal population consisting of 462 reference subjects matched on age and education. Results: One year after RT, patients reported significantly less pain and significantly fewer limitations due to their physical health compared to baseline. Compared to the normal population, patients reported significantly less pain 1 year after RT. However, patients also reported significantly less vitality, worse mental health as well as significantly more limitations due to physical and mental health 1 year after RT compared to the normal population. Conclusions: In this study, patients with PCa did not experience significant impairment in the QoL 1 year after RT compared to baseline. However, patients reported significantly worse mental health before, during and 1 year after RT compared to the normal population.