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Abstract Cooperation between Higher Education Institutions and Enterprises (HEI-E-C) is extremely relevant in regional economic development. Therefore, this study aims to understand the role of HEI in academic spin-off creation. To achieve this objective, we adopted the qualitative approach (case study method) and focused on a cooperation relation involving a Portuguese HEI and two academic spin-offs. For data collecting, several interviews with key informants and direct observation were used. Content analysis of the interviews with founders of these academic spin-offs and lecturers teaching the curricular unit of entrepreneurship in the HEI studied, the results identified some essential aspects to understand this type of cooperation (HEI-E): (1) the role of academic entrepreneurship and its importance in the growth of spin-offs for regional economic growth, (2) the influence of academic entrepreneurs’ characteristics in the process of creating a spin-off, and (3) academic motivations to create spin-offs and the benefits of cooperation with HEIs. This study also presents implications for theory and educational and business practice.
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