Universities are increasingly recognizing their entrepreneurial role, in which they actively engage in the transfer of knowledge through the establishment of university spin-offs. Following this evolution, technology transfer (TT) ecosystems within or close to many research universities have developed, uniting organizational entities (e.g. TT offices, incubators, etc.) that support entrepreneurial and startup activities. However, little research has empirically studied the TT ecosystem holistically. Using a qualitative case study approach, we compare the TT ecosystems at eight universities to understand how the characteristics of TT ecosystems differ between universities and what factors drive this variation. Specifically, we use an organizational design theoretical perspective to elucidate the activities, structure, purpose and people of TT ecosystems. Our findings point to variations between TT ecosystems, which we relate to several core drivers at the micro-, meso- and macro-levels. These drivers are important mechanisms for influencing the design of TT ecosystems to improve their effectiveness.