With healthcare budget particularly constrained in Japan, there is an urgent need to produce and to use high quality evidence to reap the greatest possible health benefits from limited available resources. An intervention is worth adopting if the health benefit it produces outweighs the foregone health benefit which could have been achieved if the additional resources associated with the intervention were to be used elsewhere in the system. The foregone benefit represents the health opportunity cost of the intervention, which informs a "cost-effectiveness threshold" and a "value based pricing" of interventions within the system. The impact and value of these policy applications depend on the extent to which they accurately reflect the health opportunity cost, which can be measured by the marginal productivity of the health system in producing health from a unit of spending. Quantifying the health opportunity cost therefore involves the estimation of the causal effects of marginal changes in healthcare expenditure on changes in health outcomes within the system. Drawing causal inferences using observational data analysis is a significant methodological challenge. This paper discusses key data and analytic methods for the quantification of the health opportunity cost for Japan and other countries.