OBJECTIVES: Multi-country trial-based cost-effectiveness analyses often assume that resource utilisation and clinical efficacy are not country-specific, and apply country-specific unit costs. We applied econometric methods to estimate country-specific cost-effectiveness, adjusting for differences in incremental resource utilisation and case mix across countries. Results with and without adjustment are compared and methods described. METHODS: The TARGET multinational trial compared cure within 21 days for patients with CAP between sequential IV/PO moxifloxacin monotherapy and standard comparators. Unit costs were available for 4 countries (France, Germany, Spain, UK) among 10. A previously published framework, based on a system of regression equations, was used to determine treatment impact on resource use and outcome by country, controlling for baseline characteristics. Clinical efficacy was held constant across countries, but the impact of cure on resource utilisation was allowed to vary. Bootstrapping was also used to estimate uncertainty around country-specific cost-effectiveness results. RESULTS: No significant inter-country variation in clinical efficacy was observed (p=0.9843). Treatment increased the probability of cure by 5% and the impact of cure on resource use varied significantly across countries (p<0.0001). However between-country differences in incremental resource utilisation were not detected statistically (p=0.7759) so that unadjusted analysis was also a possible approach. Using country-specific unit prices, average incremental costs per patient non-adjusted and adjusted were €-266 and €-436 for Germany, €-381 and €-543 for France, €-281 and €+126 for Spain, €-360 and €-1192 for UK. The probability that moxifloxacin is cost-saving was 97% for Germany, 95% for France, 90% for Spain and 87% for the UK in the non-adjusted analyses compared to 99%, 66%, 41% and near 100%. CONCLUSIONS: Where study treatments impact resource use differently across countries or country-specific CEA is desired, adjusted results can differ substantially. Although improved country-specificity is associated with increased variation in cost, country-specific cost-effectiveness measures may be more informative.