Public policies focusing on the higher education landscape often pursue a paradigm shift among universities that may ultimately lead to the transformation towards entrepreneurial universities. The purpose of this paper is to examine whether a higher education policy-induced transformation significantly influenced regional high-technology entrepreneurship. We thereby focus on the German Excellence Initiative, a higher education policy intervention designed to foster and support the transformative change of German universities towards an entrepreneurial paradigm. Our results reveal that the German Excellence Initiative had a positive and significant impact on regional high-technology entrepreneurship. Our results further show that the higher the interaction with industry, the more conducive universities become for regional high-technology entrepreneurship. In addition, universities’ overarching scientific focus decisively affects regional high-technology entrepreneurship. Based on our results, we conclude our paper by outlining implications for policy makers, high-technology entrepreneurs and university managers as well as present future avenues for research.