This paper empirically explores the important determinants for the creation of science-based spin-offs. We propose a model in which human capital, technology-based determinants and institutional determinants affect the spin-off creation process. The data are drawn from the BioPartner First Stage Grant, a seed fund to stimulate academic spin-offs in the life sciences. The unique data set covers 68 life sciences spin-off projects. This study explores the determinants of success of these spin-offs in three phases of the spin-off creation process and for the overall process. Empirical evidence shows that an attracting an experienced CEO into the venture positively influences the spin-off creation and leverages the effect of the spin-offs' scientific quality. Furthermore, we find evidence for the role of product potential, Intellectual Property (IP) position and industry experience, which vary during the spin-off creation process. Finally, we discuss managerial and policy implications.Reference to this paper should be made as follows: van der Steen, M., Ortt, R. and Scholten, V. (2010) 'Exploring determinants of life sciences spin-off creation: empirical evidence from the Netherlands', Int.