OBJECTIVES: A recent randomized 2x2 phase III trial compared oral capecitabine + IV oxaliplatin (XELOX), IV 5-FU/LV/oxaliplatin (FOLFOX-4), XELOX+bev, and FOLFOX-4+bev as first-line therapy for MCRC. FOLFOX-4 was the regulatory control. XELOX was non-inferior to FOLFOX-4 for progression-free survival, and bev-containing regimens were superior to comparison arms. This economic analysis compared expected costs in XELOX vs. FOLFOX-4 arms in an Italian hospital setting from a payer and societal perspective. METHODS: Direct medical and indirect cost estimates (for patient time and travel) were compared. Resource use and patient time were estimated based on trial data and protocols. Data collected during the trial and used in the analysis were as follows: no. of visits / duration of drug administration, central venous access management, treatment of adverse events (AE) including hospital days for treatment-related AEs and total hours of ambulatory encounters. Unit costs were based on hospital costs and other published sources. RESULTS: Total direct medical cost estimates were higher for bi-weekly FOLFOX-4 vs. 3-weekly XELOX: €17,900 vs. €10,900. XELOX had higher drug costs while FOLFOX-4 had higher drug administration costs, with about 15 more visits on average per patient. Costs for hospitalization and ambulatory encounters were slightly lower for FOLFOX-4 (€500 vs. €800); other medications and venous access were slightly higher for FOLFOX-4 (€5000 vs. €2000). Similar patterns held for FOLFOX-4+bev vs. XELOX+bev (total direct medical cost estimates €33,100 vs. €25,000). Indirect time cost estimates were lower with XELOX due to fewer cycles and visits: estimated savings range from €9,000 – €11,000. CONCLUSION: XELOX is cost-saving from both payer and societal perspective in comparison to FOLFOX-4.