Many countries have introduced health impact assessment (HIA) at the national, regional, or local levels. In France and in Québec, there is increasing interest in using HIA to inform decision-makers and influence policies, programs, and projects. This paper aims to compare HIA implementation models in two regions: Nouvelle-Aquitaine (France) and Montérégie (Québec, Canada) using a case study methodology. The objective is to gain a better understanding of the similarities and differences in the approaches used to achieve the operationalization of HIA. The methodological approach involves four steps: (1) design of an analytical framework based on the literature; (2) exchanges within the research team and review of documents concerning the two implementation strategies under study; (3) development of the case studies based on the proposed framework; and (4) cross-comparison analysis of the case studies. The findings show that the two regions share certain similarities, including the strong commitment and political will of the public health organizations involved and a well-established culture of engaging in intersectoral action with municipal partners. Differences mainly concern their different approaches to implementing HIAs in accordance with the regional policies and the organizational and administrative contexts in place. This study identifies potential avenues for supporting the practice of HIA at the municipal level.