In the last decades a deep process of institutional reforms and economic reorganization took place in central and eastern EU countries (CEE). These changes occurred in a context of general economic integration. On the one hand, the European Union enlargement programme was launched and all CEE countries applied to become EU member between 1994 and 1996. On the other hand, the globalization of the world economy characterized this historical phase. This article explores to what extent openness to global markets mediated the impact of EU integration on the economic performance of CEE regions in different periods. The periods examined are defined by the main institutional changes that occurred on the road towards EU integration. Results show that globally open regions performed better than the others, at least in the first two periods analyzed.