Innovation in the medical technology (med tech) industry has a major impact on well-being in society. Open innovation has the potential to accelerate the development of new or improved healthcare solutions. Building on work system theory (WST), this paper explores how a multi-sided open innovation platform can systematically be established in a German med tech industry cluster in situations where firms had no prior experience with this approach. We aim to uncover problems that may arise and identify opportunities for overcoming them. We performed an action research study in which we implemented and evaluated a multi-sided web-based open innovation platform in four real-world innovation challenges. Analyzing the four different challenges fostered a deeper understanding of the conceptual and organizational aspects of establishing the multi-sided open innovation platform as part of a larger work system. Reflecting on the findings, we developed five design principles that shall support the establishment of multi-sided open innovation platforms in other contexts. Thus, this paper contributes to both theory and practice.