OBJECTIVES: To compare costs and effectiveness of afatinib versus gefitinib, as first line treatment of patients with locally advanced or metastatic epidermal growth factor receptor mutation-positive (EGFR+) non-small cell lung cancer (NSCLC) in the Brazilian private healthcare system. METHODS: A disease cohort model was used to estimate 7-year progression-free life years (PFLY), life years (LY), Quality-adjusted life years (QALY) and clinical outcomes of afatinib versus gefitinib in the Brazilian setting. The model was fit using partitioned survival data from the LUX-Lung 1, 3 and 6 trials, safety data from the LUX-Lung 1 and 3 trials, and utilities from the LUX-Lung 6 and LUCEOR trials. Comparative effectiveness versus control was estimated using Bayesian indirect treatment comparison. Resource use was estimated by an expert panel consisting of Brazilian oncologists and parameterized using cost estimates from official Brazilian databases. Indirect costs were not considered in this evaluation. Costs and benefits were discounted at a 5% annual rate. RESULTS: Base case analysis showed that afatinib was associated with increased progression free survival (0.53 PFLY), increased survival (0.37 LY) and higher quality of life (0.34 QALY) and increased cost (BRL 24,890; 1USD = BRL3,483) versus gefitinib, resulting in an incremental cost-effectiveness ratio of BRL 46,709/PFLY, BRL 67,548/LY and BRL 73,757/QALY. Considering 3 PIB per capita as a threshold (BRL 86,628 per PFLY, LY or QALY), afatinib is a cost-effective technology versus gefitinib. Sensitivity analyses indicated that the conclusion was robust across relevant scenarios. CONCLUSIONS: Findings suggest that afatinib is a cost-effective option versus gefitinib as first line treatment in EGFR+ NSCLC patients under the Brazilian private healthcare system.