To address macro-social and economic determinants of health and equity, there has been growing use of intersectoral action by governments around the world. Health in All Policies ( HiAP) initiatives are a special case where governments use cross-sectoral structures and relationships to systematically address health in policymaking by targeting broad health determinants rather than health services alone. Although many examples of HiAP have e-merged in recent decades, the reasons for their successful implementation-and for implementation failures-have not been systematically studied. Consequently, rigorous evidence based on systematic research of the social mechanisms that have regularly enabled or hindered implementation in different jurisdictions is sparse. We describe a novel meth-odology for explanatory case studies that use a scientific realist perspective to study the implementation of HiAP. Our methodology begins with the formulation of a conceptual framework to describe contexts, social mechanisms and out-comes of relevance to the sustainable implementation of HiAP. We then describe the process of systematically explai-ning phenomena of interest using evidence from literature and key informant interviews, and looking for patterns and themes. Finally, we present a comparative example of how Health Impact Assessment tools have been utilized in Swe-den and Quebec to illustrate how this methodology uses evidence to first describe successful practices for implementa-tion of HiAP and then refine the initial framework. The methodology that we describe helps researchers to identify and triangulate rich evidence describing social mechanisms and salient contextual factors that characterize successful prac-tices in implementing HiAP in specific jurisdictions. This methodology can be applied to study the implementation of HiAP and other forms of intersectoral action to reduce health inequities involving multiple geographic levels of govern-ment in diverse settings.