Evidence produced by multinational trial-based cost-effectiveness studies is often used to inform decisions concerning the adoption of new healthcare technologies. A key issue relating to the use of this type of evidence is the extent to which trial-wide economic results are applicable to every single country participating in the study. We consider what role cost-effectiveness analysis alongside multinational trials should have in assisting reimbursement decisions at jurisdiction and national levels. Using the proposed framework as a benchmark to evaluate their relative pros and cons, we then describe and review the statistical approaches used in the multinational trial-based cost-effectiveness literature. The results of the review are used to define the desirable characteristics a statistical method for the analysis of data collected from different jurisdictions should have in order to be consistent with the proposed framework. It is argued that Bayesian hierarchical models that use both patient- and country-level information are the most appropriate tool to analyse multinational trial-based cost-effectiveness data and facilitate the between-country generalizability assessment of the study findings. The merits of each approach are discussed, highlighting problems and limitations, in order to identify areas of future research.