Background: Strengthening health-care effectiveness, increasing accessibility and improving resilience are key goals in the upcoming European Union health-care agenda. European Collaboration for Health-Care Optimization (ECHO), an international research project on health-care performance assessment funded by the seventh framework programme, has provided evidence and methodology to allow the attainment of those goals. This article aims at describing ECHO, analysing its main instruments and discussing some of the ECHO policy implications. Methods: Using patient-level administrative data, a series of observational studies (ecological and cross-section with associated time-series analyses) were conducted to analyze population and patients' exposure to health care. Operationally, several performance dimensions such as health-care inequalities, quality, safety and efficiency were analyzed using a set of validated indicators. The main instruments in ECHO were: (i) building a homogeneous data infrastructure; (ii) constructing coding crosswalks to allow comparisons between countries; (iii) making geographical units of analysis comparable; and (iv) allowing comparisons through the use of common benchmarks. Conclusion: ECHO has provided some innovations in international comparisons of health-care performance, mainly derived from the massive pooling of patient-level data and thus: (i) has expanded the usual approach based on average figures, providing insight into within and across country variation at various meaningful policy levels, (ii) the important effort made on data homogenization has increased comparability, increasing stakeholders' reliance on data and improving the acceptance of findings and (iii) has been able to provide more flexible and reliable benchmarking, allowing stakeholders to make critical use of the evidence.