OBJECTIVES: The objectives of this study were to explore how cross-country differences in culture, values and institutional context influence the methods and use of HTA/EE and to provide insights for those countries considering expanding the role of economic evaluation. METHODS: The countries studied were France, Germany, Italy, Spain and the United Kingdom. They are the five largest member states in the European Union and exhibit considerable differences in the financing and organization of health care and the methods and use of HTA/EE. A literature review was undertaken to locate published papers discussing the use of HTA/EE in the five countries, or discussing possible reasons for differences in approach.  RESULTS: The main values identified in the literature that influence the methods and use of HTA/EE are equity, efficiency, need and personal responsibility. The balance of importance attached to these values also influences the organization and financing of health care. National health services emphasise universality and equity and the existence of a fixed budget. Social health insurance systems emphasise plurality,  liberty and solidarity and place less emphasis on a fixed budget. The other major factors influencing the methods and use of HTA/EE is the administrative tradition being followed in the country concerned and the attitudes towards centralization/regionalization.  The ‘Anglo-American’ tradition followed in the UK encourages independent action on the part of decision-makers and transparency in decision-making. The ‘Napoleonic ‘ tradition followed in southern Europe encourages law making and the internalization of public decision-making, sometimes at the expense of transparency. The more regionalized a country is, the harder it is to establish a comprehensive and consistent approach to HTA/EE. CONCLUSIONS: Culture, values and institutional context have a major influence on the methods and use of HTA/EE in European countries. These findings should inform policies aimed to foster the use of HTA/EE in decision-making.