This contribution offers an overview of the ‘third research paradigm’, its historical roots and its relevance for health informatics. Using illustrative studies, we explore the concepts of triangulation and integration of quantitative and qualitative data and refute common philosophical objections to mixing different types of knowledge. We consider how the mixed method paradigm relates to two programme design and evaluation frameworks that are important for health informatics: realist evaluation and Theory of Change. We discuss how to manage practical challenges to this approach and explain how mixed method studies support an evidence-based approach to real world policy, planning and investment decisions.