This paper analyses the motivations of academic entrepreneurs to create new firms based on their research results (academic spin-offs). We propose a model to analyse entrepreneurial motivation that comprises six major dimensions: personal, relating to the business opportunity, to scientific knowledge, to the availability of resources to create a new firm, to the organization of origin, and to the social environment. The model is tested based on information from a survey administered to 152 Spanish academic entrepreneurs. Our results show that entrepreneurial opportunity is not part of the entrepreneurial motivation, but is of the utmost importance to academic entrepreneurs. Also, we find the desire to develop scientific knowledge coupled with problems related to their transfer in the immediate environment is the main driver of entrepreneurial activity in the academia.