OBJECTIVES: The aim of the study was to analyze the cost-effectiveness of cetuximab compared to bevacizumab, both in combination with cytotoxic chemotherapy (folinic acid, fluorouracil and irinotecan, FOLFIRI), for first-line treatment of RAS wild-type metastatic colorectal cancer, under the public perspective in Brazil. METHODS: A cost-effectiveness analysis has been developed based on a Markov model, comparing the use of cetuximab+FOLFIRI versus bevacizumab+FOLFIRI. Only 2014 direct medical costs were considered in the analyses and outcomes were measured in terms of life years saved. Efficacy data were obtained from the recently published clinical trial FIRE-3, a head-to-head trial between cetuximab+FOLFIRI and Bevacizumab+FOLFIRI, and costs were obtained from national databases, reflecting the perspective of the public healthcare sector in Brazil as a third party payer. Costs and outcomes were discounted to present value at a 5% annual rate. The time horizon considered 10 years. The total number of patients was calculated by the number of patients currently receiving chemotherapy who would be considered RAS wild-type and eligible to use cetuximab. RESULTS: In a 10 years time horizon, the use of cetuximab + FOLFIRI achieved clinical gains of 0,51 life years saved compared to bevacizumab + FOLFIRI, with an average cost reduction of R$1,953 per patient. Cetuximab was shown to be a dominant therapy compared to bevacizumab, saving resources up to BRL 14,450,940.00 considering 5,171 patients  in 2015. CONCLUSIONS: The use of cetuximab as first-line treatment for wild-type RAS metastatic colorectal cancer has shown significant and clinically meaningful benefits while being cost-saving to the Brazilian public healthcare system.