OBJECTIVES: The randomized CHAT trial (N=222) comparing trastuzumab and docetaxel either with capecitabine (HTX) or without (HT) as first-line therapy for HER2+mBC, demonstrated significantly superior progression-free survival (PFS) and a trend towards improved overall (OS)survival with HTX after 2 years of follow-up.  This economic analysis was conducted to evaluate the cost-effectiveness of adding capecitabine to HT in these patients in Spain, France and Italy. METHODS: A Markov-model was constructed to estimate OS and PFS for a 10-year time horizon using a parametric extrapolation of PFS data from the CHAT-trial and identical transition probabilities from progression to death in both arms. Costs for drug use, administration, treatment of adverse events and supportive care were included. A probabilistic sensitivity analysis was conducted to account for uncertainty. RESULTS: Adding capecitabine to HT resulted in 0.4 (95%CI: 0.03–0.84) additional years of PFS and 0.4 (95%CI: 0.0–0.73) additional life years gained (LYG). Mean total costs increased by €5,500 (95%CI: -6,012–17,918) in the HTX-arm for France, €4,200 (95%CI: -5,700–14,690) for Spain and €3,100 (95%CI: -3,626–10,770) for Italy. This increase was mainly due to costs for capecitabine and trastuzumab (higher cumulative dose in the HTX-arm), although approximately 40% of these additional costs were compensated by reduced dosage and costs from docetaxel. Costs per PFS-year amounted to €13,000 (France), €10,000 (Spain) and €7,500 ( Italy). Costs per LYG were €15,400 (France), €11,900 (Spain) and €8,900 (Italy). More patients in the HT-arm (18 vs. 10) received trastuzumab for the treatment of progression. These additional costs were not included in the analysis. CONCLUSIONS: HTX significantly improved outcomes for patients compared with HT. A partial cost-offset due to the reduction of docetaxel dosage contributes to the overall cost-effectiveness of adding capecitabine to HT for first-line treatment of HER2+mBC, even without considering costs for the treatment of progression.