ABSTRACT: Background:Socio-economic status from early life has been linked to cardiovascular disease risk, but the impact of life-course socio-economic trajectories, as well as the mechanisms underlying social inequalities in cardiovascular disease risk, is uncertain. Objectives:We assessed the role of behavioural, psychosocial and physiological (including inflammatory) factors in the association between life-course socio-economic status and cardiovascular disease mortality in older adults. Methods:Participants were 7846 individuals (44% women) from the English Longitudinal Study of Ageing, a representative study of individuals aged???50 years, established in 2002-03. Comprising four indicators of socio-economic status (father's social class, own education, occupational position and wealth), we computed an index of socio-economic trajectory and a lifetime cumulative socio-economic score. Behavioural (smoking, physical activity, alcohol consumption, body mass index) and psychosocial (social relations, loneliness) factors, physiological (blood pressure, total cholesterol, triglycerides) and inflammatory markers (C-reactive protein, fibrinogen), measured repeatedly over time, were potential explanatory variables. Cardiovascular disease mortality was ascertained by linkage of study members to a national mortality register. Mediation was calculated using the traditional 'change-in-estimate method' and alternative approaches such as counterfactual mediation modelling could not be applied in this context. Results:During the 8.4-year follow-up, 1301 study members died (438 from cardiovascular disease). A stable low-social-class trajectory was associated with around double the risk of cardiovascular disease mortality (hazard ratio; 95% confidence interval: 1.94, 1.37; 2.75) compared with a stable high social class across the life course. Individuals in the lowest relative to the highest life-course cumulative socio-economic status group were also more than twice as likely to die of cardiovascular disease (2.57, 1.81; 3.65). Behavioural factors and inflammatory markers contributed most to explaining this gradient, whereas the role of psychosocial and other physiological risk factors was modest. Conclusions:In a population-based cohort of older individuals living in England, we provide evidence that disadvantage across the life course is linked to cardiovascular mortality. That behavioural factors and inflammatory markers partially explain this gradient may provide insights into the potential for intervention.