Background and Purpose: Whole-brain radiotherapy (WBRT) is the most common treatment for brain metastases. Most of these patients have a poor survival prognosis. Therefore, a short radiation program is preferred, if it provides a similar outcome as longer programs. This study compares 20 Gy in five fractions (treatment time: 1 week) to longer programs, with higher doses including 30 Gy in ten fractions (2 weeks) and 40 Gy in 20 fractions (4 weeks). Patients and Methods: Data regarding 1,085 patients treated with WBRT for brain metastases were retrospectively analyzed. 387 patients received 20 Gy in five fractions, and 698 patients received higher doses (30 Gy in ten fractions, n = 527, or 40 Gy in 20 fractions, n = 171). In addition, eight potential prognostic factors were investigated including age, sex, Karnofsky Performance Score (KPS), tumor type, interval from tumor diagnosis to WBRT, number of brain metastases, extracranial metastases, and recursive partitioning analysis (RPA) class. Subgroup analyses were performed for each RPA class individually. Results: The WBRT schedule had no significant impact on survival (p = 0.415). On multivariate analysis, improved survival was significantly associated with age ≤ 60 years (risk ratio [RR]: 1.28; p < 0.001), KPS ≥ 70 (RR: 1.73; p = 0.002), lack of extracranial metastases (RR: 1.27; p = 0.007), interval from tumor diagnosis to WBRT > 8 months (RR: 1.19; p = 0.011), and lower RPA class (RR: 1.56; p < 0.001). The subgroup analyses for each RPA class did not reveal a significant association between WBRT schedule and survival. Conclusion: Short-course WBRT with 20 Gy in five fractions is preferable for most patients, because it is associated with similar survival as longer programs and is less time-consuming.