Objective To evaluate survival following afatinib (AF) and erlotinib (ER) treatment in advanced del19 lung adenocarcinoma (AD19LA) with asymptomatic brain metastasis (ABM) after pemetrexed-cisplatin chemotherapy (PCC). Methods Data were retrospectively analysed from individuals with AD19LA and ABM after PCC who received AF or ER for 2 years or until intolerable adverse events (AEs), withdrawal, or death. The primary outcome was survival; secondary outcomes were AEs. Results The final analysis included 174 AD19LA individuals (AF: n = 86; ER: n = 88) with a median follow-up of 24.2 months (IQR 2.1-28.3). Significant differences in overall survival (16.2 months [95%CI 15.4-17.1] for AF vs 7.2 months [95%CI 6.3-8.1] for ER) (HR 0.50, 95%CI 0.36-0.71, p<0.0001) and median progression-free survival (9.4 months [95%CI 8.5-9.7] for AF vs 5.6 months [4.7-6.2] for ER) (HR 0.66, 95%CI 0.47-0.94, p=0.02) were observed between the groups. Rates of all-grade AEs were 82.5% for AF and 72.7% for ER, and rates of grade >= 3 AEs were 37.2% for AF and 34.0% for ER. Conclusion Compared with ER, AF treatment may be more beneficial in terms of survival in the management of AD19LA after PCC with a tolerable safety profile.