OBJECTIVES: There is a renewed interest in health system indicators. In 1976 a measure of quality of healthcare, amenable mortality, was introduced by Rutstein. This indicator is based on the concept that deaths from certain causes should not occur in the presence of timely and effective healthcare. In the project "Amenable mortality in the European Union: toward better indicators for the effectiveness of health systems" (AMIEHS), we introduce a new approach to the selection of indicators of amenable mortality. METHODS: Based on predefined selection criteria and a broad review of the literature on the effectiveness of medical interventions, a first set of potential indicators of amenable mortality (causes of death) was selected. The timing of the introduction of medical innovations was established through reviews and questionnaires sent to national experts from seven participating European countries. The preselected indicators were then validated by a trend analysis that identified associations between the timing of innovations and cause-specific mortality trends and by a Delphi-procedure. RESULTS: After a short review of previous lists of amenable mortality indicators and a detailed description of the innovative procedure in the AMIEHS project we present a list of 14 causes of death that passed our selection criteria. We illustrate our empirical validation of these indicators using the examples of peptic ulcer and renal failure. CONCLUSIONS: The innovation developed in the AMIEHS study is a rigorous new approach to the concept of amenable mortality that includes empirical validation. Only validated indicators can be successfully used to assess the quality of healthcare systems in international comparisons.