The main objective of the study is to examine whether certain factors linked to institutional capabilities as well as financial, human capital and infrastructure attributes have an impact on the creation of university spin-offs in Spain. We tested this using a negative binomial regression and a cluster analysis on a sample of 45 public Spanish universities for the year 2008. Our results reveal that the accumulated knowledge derived from previous experience in spin-off creation matters, giving support to the argument about the presence of knowledge spillovers linked to the creation of spin-offs. We also find that universities more actively involved in patenting create more spin-offs. Throughout our analysis we identified different patterns followed by Spanish universities in terms of knowledge transfer activities: universities actively involved in knowledge transfer activities, universities lacking an entrepreneurial culture that bridges the gap between research and academic entrepreneurship, and universities that need to consolidate their research and their entrepreneurial culture. Mimicking policies in different institutional settings without the proper adaptation do not help knowledge transfer activities within universities. Rather, policies aimed at improving knowledge transfer activities should be designed according to the specific profile of the targeted group of beneficiaries.