BackgroundHealth economic evaluation attempts to provide a rational and coherent framework to help policy makers to decide which health interventions to fund by comparing the differences in costs and outcomes between alternative options. Mathematical models are used to simplify complex realities; as such, there are always uncertainties associated with the model structure and inputs, and hence with the model results. It is thus important to be able to describe and justify the model structure and inputs used. The structural development of public health economic models is currently based on ad hoc non-transparent methods that are highly dependent on the modeller. We present a conceptual modelling framework to guide modellers when developing the structure of these models. MethodsTwo scientific literature reviews and qualitative research informed the framework. The reviews explored key challenges in public health economic modelling and conceptual modelling frameworks within the broader literature. They were undertaken with a systematic, iterative search method in accordance with UK National Institute for Health and Clinical Excellence technical support document guidance, including citation, reference, and key author searching within Medline, Scopus, and Web of Science. The qualitative research aimed to understand modellers' experiences with developing model structures and their views about the benefits and barriers of the use of a conceptual modelling framework. This involved a three-phase approach: tracking of the development of a Public Health economic model by in-depth interviews with the two modellers involved, and attendance at meetings between the project team and stakeholders, during which notes were made on the model development process; systematic analysis of our own notes from a previous public health economic project; and arrangement of a focus group with public health modellers from five different centres within the UK, identified purposively through relevant publications. Topic guides were developed for the interviews and focus group, using learning from the literature reviews for the former, and analysis of the interview data for the latter, including asking participants whether they agreed or disagreed with some of the interviewee responses. Each sentence from the transcripts and notes was copied into emergent categories in Excel. The analysis began after the first set of interviews. After coding of the first three interviews was complete, similar categories were grouped into themes, which were used for subsequent analysis. Similar and conflicting views between modellers were captured by the framework. A draft version of the framework was piloted with a case study of the cost-effectiveness of interventions for diabetes prevention to further develop it. FindingsWe identified three key principles for the conceptual modelling framework: a systems approach to public health economic modelling is most appropriate (ie, the system should be understood as a whole taking into account feedback loops and unintended consequences); a thorough documented understanding of the problem is valuable before development of the model structure to be able to communicate with stakeholders and justify the structure that is developed; and communication with stakeholders and members of the team throughout model development is important. The framework has four stages. First, identification of relevant stakeholders. Second, alignment of the framework with the decision making process. Third, understanding of the problem, which involves the development of a causal diagram of the problem and establishing current resource pathways. Fourth, development and justification of the model structure, which includes selection of the model interventions, setting of the model boundary and the level of detail, identification of the model type, and provision of a qualitative description of the quantitative model. InterpretationNon-prescriptive suggestions around how modellers might undertake each of the stages above are provided within the framework. This framework aims to improve the scope, quality, and communication of public health economic models to help decision makers to make appropriate policy decisions. FundingThis work is produced by HS under the terms of a doctoral research training fellowship issued by the NIHR.