Innovations in health care are often characterized by complexity and fuzzy boundaries, involving both the elements of the innovation and the organizational structure required for a full implementation. Evaluation in health care is traditionally based on the collection and dissemination of evidence-based knowledge stating the randomized controlled trial, and the quasi-experimental study design as the most rigorous and ideal approaches. These evaluation approaches capture neither the complexity of innovations in health care, nor the characteristics of the organizational structure of the innovation. As a result, the reasons for innovations in health care not being disseminated are not fully explained. The aim of the paper is to present a design – evaluation framework for complex innovations in health care in order to understand what works for whom under what circumstances by combining design theory and realist evaluation. The framework is based on research findings of a case study of a complex innovation, a health care quality register, in order to understand underlying assumptions behind the design of the innovation, as well as the characteristics of the implementation process. The design - evaluation cycle is hypothesized to improve the design and implementation of complex innovation by using program/kernel theories to develop design propositions, which are evaluated by realistic evaluation, resulting in further refinement of program/kernel theories. The goal of the design – evaluation cycle is to provide support to implementers and practitioners in designing and implementing complex innovations in health care. As a result, the design – evaluation cycle could provide opportunities of improving dissemination of complex innovations in health care.