This study compared the therapeutic effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with that of EGFR-TKI plus whole brain radiotherapy (WBRT) on patients with EGFR mutation-positive lung adenocarcinoma and brain metastases. A total of 139 patients with lung adenocarcinoma and brain metastases treated with first-line EGFRTKI therapy from September 2008 to December 2017 were enrolled in this study. The study endpoints were intracranial time to progression (TTP) and overall survival (OS). The effects of clinical pathological parameters and EGFR gene status on the study endpoints were compared. The results showed that the intracranial TTP was significantly longer in EGFR-TKI plus WBRT group than in EGFR-TKI group (median 30.0 vs.18.2 months, χ2=10.824, P=0.001), but no significant difference in the OS was noted between the two groups (median 48.0 vs. 41.1 months, χ2=0.012, P=0.912). Also, there was no statistically significant difference in the OS between patients treated with early and late radiotherapy (P=0.849) and between those with asymptomatic and those with symptomatic intracranial metastases (P=0.189). The OS and intracranial TTP of patients with intracranial oligometastases (≤3 metastatic sites) were not significantly different from those of patients with multiple intracranial metastases (P=0.104 and P=0.357, respectively), and exon 19 and exon 21 mutations didn’t show significant effects on the OS and intracranial TTP of patients (P=0.418 and P=0.386, respectively). In conclusion, there was no statistically significant difference in the OS between the EGFR-TKI alone group and EGFR-TKI plus WBRT group. However, simultaneous use of WBRT was found to significantly prolong intracranial TTP and improve cerebral symptoms, and thus EGFR-TKI and WBRT combined may be clinically beneficial for patients with EGFR mutation-positive lung adenocarcinoma and brain metastases.