Purpose: The aim of this prospective cohort study was to determine the outcome and quality of life (QoL) for patients with brain metastases treated with whole-brain radiotherapy (WBRT). Materials and Methods: WBRT was given to 162 patients. Treatment outcome was reported through telephone consultation at four and eight weeks after the last fraction of the treatment. Treatment outcome was scored as a benefit when patients reported positively on the question whether radiotherapy of the whole brain did relieve their complaints. Patients who scored the treatment as beneficial were categorized as responders. The European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ-C15-PAL was scored at day 0 and eight weeks after the last fraction of WBRT. Results: Patients who were alive after 2 months and reported benefit from treatment had a median survival of 8.1 months compared with 2.9 months for patients who reported no benefit. Forty-three patients died within two months (27%). Median overall survival was 3.5 months. Improvement of neurological symptoms was the most commonly reported benefit of the treatment. The responders had significantly better sleep (p = 0.032) and were less tense (p = 0.014). The nonresponders were also less tense (p = 0.042), but had less appetite (p = 0.023), felt weaker (p = 0.011), and experienced more fatigue (p = 0.001). Conclusions: WBRT is effective in a selected group of patients. Forty-nine percent of the patients surviving two months reported benefit from the treatment, resulting in a significantly increased survival rate for this group. However, 27% of patients died within two months. QoL increased in responders, but decreased in nonresponders.