Background: In the Netherlands, there is a substantial social gradient in mortality: individuals with higher socio-economic status are more likely to live longer lives than those with lower socio-economic status. There is evidence that this social gradient has widened since the mid-twentieth century, although why this has occurred is poorly understood. Cardiovascular disease (CVD) provides a particularly useful case study for understanding the mechanisms underlying this widening gradient. While CVD was historically the leading cause of death in the Netherlands, improvements in prevention and treatment have decreased CVD mortality, even as socio-economic inequalities in CVD mortality have increased. In this project, I aim to identify and test the mechanisms driving widening socio-economic inequities in CVD mortality over the last 75 years. Methods and analysis: This project uses mixed-methods. First, in participatory workshops, key stakeholders, e.g. policymakers, healthcare professionals, patient representatives, and individuals with lived experience of poverty, will co-create a conceptual model outlining the explanations linking socio-economic status and CVD in the Netherlands. Second, the conceptual model will provide the structure for the microsimulation, with the former defining which mechanisms will be represented in the latter. The microsimulation will maintain a common model structure across time, although population characteristics and individual trajectories will change to reflect successive twenty-year periods from the 1950s until today. The microsimulation will be validated by comparing simulated outcomes with historical data. Counterfactual scenarios will then be used to estimate the relative contribution of different mechanisms to the widening of socio-economic inequalities in CVD mortality. Ethics and dissemination: This project has been approved by the Social Sciences Research Ethics Committee of Wageningen University (approval number 2026-203). Participants will provide informed consent prior to participation. The microsimulation code will be made openly available, and findings will be disseminated through open-access publications, conference presentations, and a public summary co-designed with stakeholders.