The last decades registered a significant increase in Research Infrastructures (RIs) everywhere and in Europe. The EU supports these projects and their activities by implementing strategies and allocating financial resources for these costly projects. Although RIs main goal is to foster science, they produce relevant effects that go beyond scientific output including economic output, innovation, and social impact. These effects take place simultaneously at different geographic levels: regional, national, and international. RIs’ hosting regions absorb a significant part of them. This phenomenon is the object of a stream of literature that analyses the several effects that single RIs have on the economy and society. However, little attention is paid to the aggregate dimension of these effects at the regional level and how it changes in different regional contexts. This work contributes to the main literature on RIs socio-economic effects by disentangling the aggregate economic growth effect driven by RIs in EU NUTS 2 regions for two periods: 2001-2020 and 1981-2020. The empirical analysis is carried out on an original database with information about 667 RIs. A spatial Durbin model estimates both the direct impact and spatial spillovers. The main findings suggest that RIs have a positive impact on regional economic growth over the two periods considered. However, spillover effects to neighbouring regions are not significant.