Past studies of business associations conducted in the late 1980s indicated that employers were reluctant to support devolution due to economic fears and political uncertainties. However, profound changes have altered the dominant economic and political paradigms over the course of the last three decades. Regional innovation has become a linchpin for competitive economies, whereas secession has become a skyrocketing political issue in Catalonia and Scotland, and a number of regional agencies have been settled throughout Europe, even in unitary states. Have business associations adapted to this new reality? This article examines 18 regional business associations from three Spanish regions (Catalonia, Andalusia and the Valencian Community) and three UK regions (Scotland, Wales and South West England). The first part of the article discusses six theoretical arguments linking business associations and regionalism. A general overview of the cases is offered in the second section. The third section of the article performs a fuzzy sets/Qualitative Comparative Analysis to identify the main factors that bolster the regionalisation of business associations. By way of conclusion, there are two routes towards successful regional business mobilisation. On the one hand, this happens in regions where a competent institutional arrangement has been established. On the other hand, this also happens when business associations recognise the economic and political strengths of the region while they are able to interact with regional institutions.