Abstract Background High healthcare expenditures due to population ageing and chronic complex health complaints are a challenge on a global scale. To improve the quality of healthcare, population health, and professionals’ work satisfaction and to reduce healthcare costs (Quadruple Aim), the Dutch Ministry of Health, Welfare and Sport designated nine pioneer site regions across the Netherlands. One of these pioneer sites is the integrated community approach (ICA) known as ‘Blue Care’. This article describes the design of a prospective study investigating the effects of Blue Care ICA on Quadruple Aim outcomes and a process evaluation focussing on its implementation in deprived neighbourhoods. Methods A mixed-methods approach, combining both quantitative and qualitative research methods, is applied to yield an enriched understanding of the various processes that will take place in the neighbourhoods. A prospective, quasi-experimental study is conducted within a natural experiment. Blue Care ICA is being implemented between 2017 and 2020 and research activities are taking place parallel to the implementation process. Effects of Blue Care ICA are measured at T0 (baseline), T1 (after 1 year), T2 (after 2 years) and at T3 (after 3 years) using a questionnaire. The primary outcome measure is health-related quality of life (SF-12v2), secondary outcomes are health status (EQ-5D-5 L), resilience (RS-Scale), Positive Health (Spiderweb diagram) and quality of care (grade 0–10). As part of the process evaluation, the Consolidated Framework for Implementation Research guided the formulation of process evaluation questions. Participant observations, interviews and focus groups with all stakeholders active in the Blue Care ICA will be conducted during the whole implementation period (2017–2020). Discussion The evaluation takes into account the interconnections between content, application, context and outcomes to understand how the Blue Care ICA unfolds over time in a complex, dynamic setting. Results of the effect and process evaluation will become available in 2020. Trial registration NTR 6543, registration date; 25 July 2017.