BACKGROUND Leptomeningeal carcinomatosis is a relatively rare metastatic form of non-small cell lung cancer, which can impact prognosis. There is an increasing need for selecting suitable epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors among those currently included in standard care for EGFR mutation-positive patients. We compared the efficacy of gefitinib and erlotinib in survival of patients with leptomeningeal carcinomatosis. METHODS The medical records of 269 patients who received tyrosine kinase inhibitors at a single center were retrospectively reviewed. Overall, 22 patients (8.2%) were treated with tyrosine kinase inhibitors for leptomeningeal carcinomatosis from non-small cell lung cancer with EGFR mutation between 2006 and 2016. Time to death from leptomeningeal carcinomatosis diagnosis was compared between the gefitinib and erlotinib groups. RESULTS Gefitinib and erlotinib were administrated to 5 and 17 patients, respectively. Median progression-free survival was longer in the erlotinib group than in the gefitinib group (6.60 vs 2.12 months, P = 0.07). Overall survival was more than twice as long in the erlotinib arm compared with that in the gefitinib arm (7.20 vs 2.99 months, P = 0.32). Response in patients with exon 19 deletion was better than in those with exon 21 mutation (overall survival, 7.20 and 5.62 months, respectively, P = 0.12). CONCLUSIONS Erlotinib seemed more effective than gefitinib in prolonging survival in leptomeningeal carcinomatosis from EGFR mutation-positive non-small cell lung cancer and may be particularly beneficial in patients with EGFR exon 19 mutations, warranting further studies.