OBJECTIVES: Lung cancer is the most common type of cancer over the world, from which 80-85% is non-small cell lung cancer (NSCLC). Erlotinib has been approved by FDA for first-line therapy in EGFR-mutations positive NSCLC. However the high price of drug created a large barrier in practice especially in Vietnam. This study aims to evaluate the cost - effectiveness of erlotinib versus current chemotherapy (gemcitabine/carboplatin - GC) in first-line therapy of EGFR - mutations positive NSCLC from Vietnamese healthcare payers’ perspective METHODS: A three-state Markov model has been constructed to predict expected costs and outcomes for each regimen. Only medical direct cost including cost for drug and medical services has been evaluated due to the healthcare payers’ perspective. Data of effectiveness has been retrieved from the clinical trial OPTIMAL – CTONG 0802, data of treatment cost has been estimated based on the treatment guideline of Ministry of Health of Vietnam. One-way deterministic sensitivity analysis has been conducted to evaluate the sensitivity of model. RESULTS: It has been shown that within life-time horizon, erlotinib regimen required approximately 601 million VND more than the GC regimen (884 million vs 283 million VND, respectively) with 0.75 QALY gained (1.51 vs 0.76; respectively). The ICER/QALY was accounted for 801.3 million VND per QALY gained, which is lower than 3 times of WTP of Viet Nam.  That means erlotinib was limited cost-effective compared with GC regimen in first-line therapy of advanced EGFR-mutations positive NSCLC from healthcare payers’ perspective. One-way deterministic sensitivity analysis showed that the price of erlotinib, gemcitabin and carboplatin were the most influencing factors on the cost-effectiveness of erlotinib. CONCLUSIONS: Erlotinib was limited cost-effectiveness compared with GC in first-line therapy of advanced EGFR-mutations positive NSCLC. The result revealed the necessity of supports from suppliers or heath insurance agencies to enhance cost-effectiveness of erlotinib in advanced NSCLC treatment.