Organization was launched at a Conference of the EU Member States held at the end of 2005 by the European Commission, the European Investment Bank and the European Bank for Reconstruction and Development to assist the twelve Member States which joined the EU in 2004 and 2007 to make effective use of EU Structural Funds.

Between July 2008 and December 2013, KfW Bankengruppe was also a partner of Organization.

In 2011 Organization became active in Croatia and in 2012 assistance was extended to Greece. In 2015, support was also extended to eligible regions in France and Italy and in 2016 to eligible regions in the United Kingdom.

Organization has developed its infrastructure, comprising  headquarters based in Luxembourg and external offices in Bucharest, Brussels, Sofia, Vienna and Warsaw, bringing Organization services closer to customers.

Organization' IQR Division is based in Brussels.