For more than 20 years, interdisciplinary innovation research utilizes systems of innovation (SI) as a valuable core concept for analyzing innovation phenomena at large scale. Until today, this concept has not been referred to widely in information systems (IS) research. In this paper, we argue that SI may serve as a useful study subject for IS research. For analyzing and intervening into systems of IT innovation, a conceptual and methodological foundation is required. Therefore, we developed the outline of a conceptual and a methodological research framework. This framework has initially been used in a research project on the system of IT innovation for hospitals in Germany. Insights from this study were used to further improve the framework.