Given the regional disparities that historically characterize the Italian context, in this paper we propose a framework to evaluate the regional health care systems’ performance in order to contribute to the debate on the relationship between decentralisation of health care and equity. To investigate the regional health systems performance, we refer to the OECD Health Care Quality Indicators project to construct of a set of five composite indexes. The composite indexes are built on the basis of the non-compensatory Adjusted Mazziotta-Pareto Index, that allows comparability of the data across units and over time. We propose three indexes of health system performance, namely Quality Index, Accessibility Index and Cost-Expenditure Index, along with a Health Status Index and a Lifestyles Index. Our framework highlights that regional disparities still persist. Consistently with the evidence at the institutional level, there are regions, particularly in Southern Italy, which record lower levels of performance with high levels of expenditure. Continuous research is needed to provide policy makers with appropriate data and tools to build a cohesive health care system for the benefit of the whole population. Even if future research is needed to integrate our framework with new indicators for the calculation of the indexes and with the identification of new indexes, the study shows that a scientific reflection on decentralisation of health systems is necessary in order to reduce inequalities.