OBJECTIVES: XELOX (capecitabine (Xeloda) + oxaliplatin) is an effective alternative to treat metastatic colorectal cancer (mCRC) patients. This study compares the costs of XELOX and FOLFOX (5-FU + oxaliplatin) in first line therapy for patients with mCRC in Brazil. METHODS: An analytic-decision model for projecting costs of treating mCRC in Brazil was developed considering local guidelines, payer perspective and a 6-months horizon. The study was based on clinical trial data (Cassidy 2004) showed that XELOX has the same efficacy of FOLFOX but with a better safety profile. The cost data used in the analysis were obtained from public sources: Official Price List; Official Physicians Fees List and local articles published in indexed journals. For the base case a patient with 1,7m2 was considered. RESULTS: XELOX is less costly (R$ 2,295) in comparison with FOLFOX. XELOX has a higher acquisition cost which is offset by savings in medical resource utilization. Mean acquisition costs of XELOX were R$ 4,973 higher than with FOLFOX, but total hospital days for treatment-related adverse events (AEs), medication costs for treating AEs, and patient time costs were higher for FOLFOX (R$ 3,194). Multi-way sensitivity analysis was conducted to check the robustness of the results. CONCLUSION: Findings suggest XELOX as a cost-saving therapy under the payers' perspective in Brazil.