The risk of brain recurrence after whole-brain radiotherapy for metastatic disease has been infrequently reported, but quoted to be as high as 50%. These values are in the context of autopsy series or clinical trials and thus may not represent experience in routine clinical practice. This retrospective analysis was undertaken: (1) to confirm recursive analysis-based prognostic factors contributing to survival; and (2) to investigate efficacy of Gamma Knife Stereotactic Radiosurgery (GKSRS) in the poorest prognosis population. The records of 85 unselected, consecutive patients receiving whole-brain radiotherapy for brain metastases at Naval Medical Center San Diego were analyzed. Median dose of whole brain radiotherapy was 30 Gy in 10 fractions. These records were categorized by Radiation Therapy Oncology Group (RTOG) categories based on several prognostic factors. Further, analysis of 153 consecutive patients (178 treatments of 396 lesions) receiving GKSRS at the San Diego Gamma Knife Center was made for patients with Karnofsky Performance Status (KPS) < 70="" (rtog="" class="" 3).="" twenty="" patients="" were="" identified.="" median="" dose="" of="" gksrs="" was="" 17.5="" gy="" at="" the="" 61%="" mean="" isodose="" line="" for="" all="" gksrs="" patients.="" six="" patients="" experienced="" clinical="" brain="" recurrences="" after="" whole-brain="" radiotherapy;="" the="" actuarial="" risk="" of="" clinical="" brain="" recurrence="" after="" whole-brain="" radio="" therapy="" approached="" 30%="" at="" 3="" years,="" although="" few="" patients="" survived="" this="" long.="" survival="" of="" patients="" after="" whole="" brain="" radiotherapy="" alone="" by="" rtog="" category="" mirrored="" findings="" of="" other="" centers.="" patients="" in="" class="" 3="">n = 26) had a median survival in our population of 59 days. For the 20 GKSRS patients with similar performance status and clinical follow-up, the median survival was longer, but not significantly so (162 days; p = 0.467). In the off-protocol setting, clinical brain recurrence of metastatic disease after whole-brain radiotherapy occurs not infrequently in patients with otherwise long survival. The RTOG criteria well describes an extremely poor-prognosis group of patients for whom the single fraction of stereotactic radiosurgery may optimize palliation as well as or better than longer courses of conventional palliative radiotherapy.