Abstract: The existing inner socio-economic discrepancies are one of the major stumbling-blocks to the sustainable development of the Danube region and to the successful realization of its different macro-regional development programmes, strategies, and action plans. That is why it is of extreme importance to assess these discrepancies on a complex base, going beyond the analysis of single indicators. From that point of view, we suggest that sophisticated methodology and approach are needed, similar to those used to elaborate thorough European spatial development models. In order to measure the current socio-economic spatial development of the Danube regions on a complex basis, we apply author’s “Development and Prosperity Index” (DPI) calculated by using the latest available data for 8 key indicators. By contrast with the majority of the scientific studies that build their conclusions on NUTS0, or rarely on NUTS1 level analysis, our research is suited at NUTS2 level so that we can take a detailed picture of the situation in the Danube region. Another significant difference from the mainstream studies is that we concentrate predominantly on the Danube-adjacent NUTS2 regions, but not on the whole area (as defined in the EU Danube Region Strategy). That approach provides us with an opportunity to divide the study in two important stages. Firstly, we make a comparative analysis and a classification of the Danube-adjacent NUTS2 regions providing empirical evidence for the significant complex socio-economic discrepancies between them. Secondly, in a view to estimate the development role of Danube in different countries, we confront the DPI results for Danube-adjacent NUTS2 regions against those for the other regions in a given country. Although this approach is characterized with certain conditionality considering that development is a function of many diverse factors, the results of the study provide solid ground for building up adequate future policies.