This paper assesses university efficiency from a multidimensional perspective. First, an efficiency measure that incorporates knowledge transfer outputs in the objective function is proposed. Second, a cluster analysis complements the efficiency model giving a more comprehensive image of university’s performance. The empirical application considers the Spanish higher education system during 2006-2009. Results point to the presence of heterogeneous orientations among Spanish universities and that they integrate knowledge transfer in their operations at different intensities. The findings give evidence that university’s efficiency and their involvement in knowledge transfer is conditioned by regional factors related to technological development and entrepreneurial culture. Results give ammunition to the argument that effective support policies should have the capacity to be customized to fit the profile of the targeted universities and regions.