Teirlinck P. and Spithoven A. The spatial organization of innovation: open innovation, external knowledge relations and urban structure, Regional Studies. The increased use of external knowledge relations, complementary to in-house research and development, influences the way firms are organized to manage innovation. The 'new' imperative of open innovation promotes the idea that firms organize innovation, to a greater extent, in interaction with outside parties. This paper argues that both the organization of innovation as well as the use of external knowledge depends on the physical, socio-economic and cultural environment. The outcome of the analysis supports the idea that (open) innovation is spatially organized. Contrary to the expectations, innovative firms in less urbanized areas show a higher degree of openness.