OBJECTIVES: To perform a cost-effectiveness analysis of Panitumumab+FOLFOX vs Bevacizumab+FOLFOX as first-line treatment on RAS-WT mCRC patients from the Mexican public healthcare system perspective. METHODS: The evaluation was performed using a Markov model that simulates a hypothetical cohort of patients over seven health-stages in two-week transition cycles. Progression-free survival (PFS) and overall survival (OS) were used as reported in the PEAK trial. Resource use was obtained from five oncologists at four public healthcare institutions. Costs include chemotherapy, follow-up, adverse events, metastasis resection, second-line treatment, palliative care, and funeral costs. Mexican Social Security Institute costs were applied. Costs and benefits are discounted at 5% for a 10-year time line. Additionally, a cost-minimization vs Cetuximab was performed due to equivalence in OS described in the ASPECCT trial and similar values of PFS and OS reported in first line for comparable populations. RESULTS: The total costs are $1,048,009.42 for Panitumumab (mean life of 3.47 years), and $872,201.70 for Bevacizumab (mean life of 2.80 years), with a mean cost-effectiveness ratio per month of OS of $25.173 and $25.932, respectively. The 10-month projection for anti-EGFR therapies reveals a total cost of $779,873.60 for Panitumumab and $1,119,871.90 for Cetuximab, which represents savings of $339,998.30 (30.4%) per patient. CONCLUSIONS: Panitumumab as first-line treatment improves the clinical parameters of RAS-WT mCRC patients and presents a mean cost-effectiveness ratio similar to Bevacizumab in this population. Regarding to Cetuximab, Panitumumab is a cost-saving strategy, with reduction in total costs of treatment and administration for public healthcare institutions in Mexico.