Background: Risk factors and treatments for brain metastasis (BM) in patients with adenocarcinoma have not been fully profiled in previous studies because of the enrolment of patients with tumours of mixed histology. Thus, we specifically addressed the issue in patients with adenocarcinoma. Methods: Clinical data for 373 patients with pathologically confirmed adenocarcinoma were studied retrospectively. Factors including age (≤60 vs.＞60), gender (male vs. female), stage at diagnosis, T status (T1-2 vs. T3-4), N status (N0-1 vs. N2-3), epidermal growth factor receptor (EGFR) mutation status (wild-type vs. mutant) and smoking status (never vs. current) were analyzed. Results: In multivariate analysis, age (P=0.006) and N status (P=0.041) were independent risk factors for BM. In patients with BM, adding systemic therapy to local therapy improved median post-brain-metastasis survival (mPBMS) (P=0.02). However, if stratification was conducted according to the recursive partitioning analysis (RPA) classification or graded prognostic assessment (GPA) scoring, only patients in RPA class Ⅱ (P=0.020) or with GPA score 1.5-2.5 (P=0.032) could benefit from local plus systemic therapy. Those who received both pemetrexed and tyrosine kinase inhibitors (TKIs) as systemic therapies had a longer mPBMS than those who received TKIs alone, regardless of whether local therapy was applied. In patients with EGFR-sensitive mutations, TKIs therapy led to a longer mPBMS than conventional chemotherapy (P=0.002). Conclusions: Adenocarcinoma patients who were younger than 60 years of age and those with N2-3 disease have a significantly higher risk of BM. The addition of systemic therapy to local therapy can significantly prolong mPBMS, but the survival benefit confined in certain populations. Patients with opportunity to receive both pemetrexed and TKIs had the longest mPBMS.