Background: Evidence supports the implementation of primary prevention and health promotion (PP&HP) activities but primary care (PC) professionals show resistance to implementing these activities. The aim was to synthesize the available qualitative research on barriers and facilitators identified by PC physicians and nurses in the implementation of PP&HP in adults. Methods and Findings: A systematic search of three databases was conducted and supported by manual searches. The 35 articles included were translated into each other and a new interpretation of the concepts extracted was generated. The factors affecting the implementation of PP&HP activities in PC according to professionals were fitted into a five-level ecological model: intrapersonal factors, interpersonal processes, institutional factors, community factors and public policy. At the intrapersonal level we find professionals' beliefs about PP&HP, experiences, skills and knowledge, and selfconcept. The attitudes and behavior towards PP&HP of patients, specialists, practice managers and colleagues (interpersonal factors) affect the feasibility of implementing PP&HP. Institutional level: PC is perceived as well-placed to implement PP&HP but workload, lack of time and referral resources, and the predominance of the biomedical model (which prioritizes disease treatment) hamper the implementation of PP&HP. The effectiveness of financial incentives and tools such as guidelines and alarms/reminders is conditioned by professionals' attitudes to them. Community factors include patients' social and cultural characteristics (religion, financial resources, etc.), local referral resources, mass-media messages and pharmaceutical industry campaigns, and the importance given to PP&HP in the curriculum in university. Finally, policies affect the distribution of resources, thus affecting the implementation of PP&HP. Conclusions: Research on barriers and facilitators in the implementation of PP&HP activities in multirisk management is scarce. The conceptual overview provided by this synthesis resulted in the development of practical recommendations for the design of PP&HP in PC. However, the effectiveness of these recommendations needs to be demonstrated. © 2014 Rubio-Valera et al.