The European Union Strategy for the Danube Region (EUSDR) aims to address the challenges and priorities of the region in an integrated manner, leading to concrete results and a better future for the region and its citizens. This requires that existing data and associated knowledge are readily available and easy to use by policy makers and citizens. In response to this challenge, the Danube Reference Data and Services Infrastructure (DRDSI) pilot project facilitates the exchange of open, harmonised (at the macro-region level) and well-documented data to support integrated policy-making needs. The DRDSI, as part of the JRC Scientific support to the EU Strategy for the Danube Region) builds on (i) the recent investments made and lessons learned from the implementation of the INSPIRE Directive, and (ii) involves the active collaboration of international and national stakeholders. The project also builds data sharing capacity by involving communities in collaborative and interdisciplinary networks, pilots and online tools. This JRC Science for Policy report provides information on how to establish a macro-regional data infrastructure based on the experiences of the JRC and stakeholders from the Danube region. This includes the identification of appropriate technologies as key components, and explaining the flows between existing datasets and research outputs. The report also documents experiences and provides recommendations as to how policy and technical issues could be addressed on a macro-regional scale. From that perspective the report would be of use to a broad range of stakeholders, involved in policy making, data provision and support to decision making on different levels (regional, national and international).