Flow is a mental state in which a person is fully immersed and actively involved in a task, even during extrinsically motivated activities at work. IT-mediated interruptions can disrupt flow, with ramifications for workers’ well-being and work performance. In this design science research paper, we develop and evaluate design knowledge for neuro-adaptive flow support systems. Building on foundations in flow theory, we conduct expert interviews and present a conceptual framework, three meta-requirements, and five design principles for flow support systems. We then implement the design principles in three prototypes and evaluate these prototypes in a lab experiment and a field study. With this paper on flow and IT-mediated interruptions in the work domain, we present an approach toward flow support systems that enable intelligent interruption management.