This conceptual paper contributes to the discussion of the role of regional government and regional Triple Helix constellations driving economic development and growth within regional boundaries. The impact of regionalism and subsidiarity on regional Triple Helix constellations, and the questions of governmentality, governance and institutional development at the regional level, were investigated. It is emphasized that the position of regional authorities in the structure of government and policy boundaries is best implemented at the regional level (the principles of regionalism and subsidiarity), and that localized policy practices represent a more precise view of government-industry-university interactions (the principle of governmentality). In addition, the regional Triple Helix context as a prerequisite for stakeholder engagement, enhancing innovation capabilities and entrepreneurial behaviour, was studied. The paper identifies the drivers behind regional competitiveness and economic development and investigates the positive externalities from strong Triple Helix constellations, as well as the impact of government support and institutionalized cooperation on value creation and value capture at the level of the locale. The paper offers a stylized model of the conditions for value creation and value capture, and presents a critical overview of the debates about the rationale for regional governments. Examples are drawn from Scotland, England and other, comparable parts of Europe.