Abstract: Cardiovascular diseases (CVD) are the world’s leading cause of morbidity and mortality, placing a disproportionately higher burden in populations with a low socio-economic status. Nearly 75% of premature CVD deaths are preventable. Healthy lifestyle behaviour is important in the prevention of CVD and its modifiable risk factors. However, a critical research-practice gap remains on the implementation of structured preventive interventions. Horizon 2020 funded ‘Scaling-up Packages of Interventions for cardiovascular disease prevention in selected sites in Europe and sub-Saharan Africa’ (SPICES) project aimed to implement a multicomponent intervention package in different contexts. This PhD outlines part of the SPICES project activities. The general objective of this thesis was to develop and implement a comprehensive intervention program for the primary prevention of CVD in primary health care (PHC) and community settings in Belgium. This implementation research project applied principles of participatory action research and mixed-methods evaluation, using the Consolidated Framework for Implementation Research and RE-AIM. During the implementation process, we conducted exploratory qualitative research, systematic literature review, contextual analysis, multi-method intervention development and contextualization, and formative process evaluation of the implementation. Our research activities showed that to reach vulnerable populations for prevention and to maximize intervention effectivity, programs should be delivered by multi- or interdisciplinary teams in PHC and community settings. However, the current link between PHC and the community is unclear. Moreover, Belgian general practice is urging for well-defined task descriptions for interprofessional collaboration and systematic support for the sustainable integration of practice nurses. The SPICES program consisted of two main components: 1) a CVD risk profiling component using the Non-Laboratory INTERHEART Risk Score, and 2) a coaching component ...