Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer‑related deaths in many countries. Brain metastases (BM) from NSCLC are poor prognosis, with a median survival of 6 months following whole‑brain radiotherapy. NSCLC patients harboring activating epidermal growth factor receptor (EGFR) mutations have generally responded to afatinib with good objective response rate, progression‑free survival (PFS), and overall survival (OS), and platinum‑double chemotherapy. These findings demonstrate the potential effectiveness of afatinib for the treatment of EGFR‑positive with BM. The aim of this retrospective study is to present data on the prognostic effect of afatinib versus gefitinib in an unselected population with newly diagnosed NSCLC with BM collected. Patients and Methods: Data were obtained from our electronic database from 48 patients with newly diagnosed EGFR mutative NSCLC with BM and treated from January 2007 to December 2017, in which data on EGFR mutation was all available at the time of diagnosis. Results: Thirteen of forty‑eight were treated with afatinib, and the other was treated with gefitinib. There were seven Exon 19 deletion and six were Exon 21 mutation ([p.Leu858Arg, (c.2573T>G)]:4; [p.Leu861Gln, (c.2582T>A)]:2). There was 18 Exon 19 deletion, and 16 were Exon 21 mutation ([p.Leu858Arg, (c.2573T>G)]:16) and the other one was Exon 18 mutation [p.Gly719Ser (c.2155G>A)]. There was no significant difference between two groups included PFS (afatinib: 12.0 months vs. gefitinib: 10.1 months, P = 0.766) and OS (afatinib: 20.6 months vs. gefitinib: 14.5 months, P = 0.362). Conclusion: From the K–M survival curve evaluation, neither the PFS nor OS have the statistical significance between gefitinib and afatinib. We provided a real‑world data to compare the efficacy of EGFR‑TKI in NSCLC. Due to relative small sample size, we urged large clinical trial to provide more precise results.