BACKGROUND. Nonsmall cell lung cancer (NSCLC) patients with brain metastases usually receive whole-brain radiotherapy (WBRT). Most of these patients survive for only a few months. A short course of WBRT would be preferable to longer regimens if it could provide similar survival. This retrospective study of NSCLC patients compared longer treatment programs with short-course WBRT with 5 x 4 Gy given during 5 days. METHODS. Data from 404 NSCLC patients treated with WBRT for brain metastases were retrospectively analyzed. The 140 patients who received 5 x 4 Gy given in 5 days were compared for survival with 264 patients who received either 10 x 3 Gy given in 2 weeks or 20 x 2 Gy given in 4 weeks. Seven further potential prognostic factors were investigated for survival including age, sex, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, interval from tumor diagnosis to WBRT, and RPA (recursive partitioning analysis) class. RESULTS. The WBRT regimen was not associated with survival (P = .55). On multivariate analysis, age < 60 years (vs ≥60 years, P = .020), KPS ≥70 (vs KPS < 70, P < .001), interval from tumor diagnosis to WBRT > 12 months (vs ≤12 months, P = .007), no extracranial metastases (P < .001), and RPA class 1 (vs RPA class 2 vs RPA class 3, P = .007) were significantly associated with improved survival. CONCLUSIONS. Short-course WBRT with 5 x 4 Gy appeared preferable for most NSCLC patients, as it was associated with survival similar to longer WBRT programs, and the short course was less time consuming.