A scientific approach to health informatics requires sound theoretical foundations. Health informatics implementation would be more effective if evidence-based and guided by theories about what is likely to work in what circumstances. We report on a Medinfo 2015 workshop on this topic jointly organized by the EFMI Working Group on Assessment of Health Information Systems and the IMIA Working Group on Technology Assessment and Quality Development. We discuss the findings of the workshop and propose an approach to consolidate empirical knowledge into testable middle-range theories.