This paper examines the relationship between the economic growth of European regions and their knowledge and human capital endowments. The share of adult population with tertiary education and the intensity of R&D expenditures in value-added emerge as the most effective factors enhancing the growth of GDP per capita recorded, during 1995–2002, by the regions belonging to twelve countries of the former EU15. However, while the educational variable is effective for the whole regional set, the impact of R&D is significant only for the regions that are above a given threshold of per capita GDP. Moreover, remarkable disparities arise among the regions of different countries.