The role of universities in regional innovation has evolved over the last 20 years. This evolution has seen the emergence of a third role of universities that has re-shaped and transformed their two traditional functions of teaching and research. This paper proposes a conceptual framework for analysing variation in the roles performed by universities in the development of regional innovation systems. This framework is based on the triple helix model of university, industry, government relations, the literature on university engagement and the innovation systems literature, more generally. The framework is applied to a comparative study of three non core-metropolitan universities in Australia. A number of insights and issues are drawn in regard to conceptualising the role of universities in regional systems.