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Objectives Cumulative burden of vascular risk factors (VRFs) has been linked to an increased risk of depressed mood. However, the role of age in this association is still unclear. Here, we investigated whether VRF burden is associated with levels and changes in depressed mood and whether these associations become stronger or weaker from mid- to later life. Method We used longitudinal data from 5,689 participants (52–89 years) of the English Longitudinal Study of Ageing. A composite score incorporated the presence of 5 VRFs: hypertension, diabetes, smoking, obesity, and hypercholesterolemia. Second-order latent growth models were used to test whether levels and changes of depressed mood differed as a function of baseline VRF burden, and whether these associations were moderated by age. Results Baseline VRF burden showed a small association with higher levels of depressed mood (estimate = 0.081; 95% CI: 0.024, 0.138, p = .005). This association varied with age, such that it was stronger in midlife compared to later life (estimate = −0.007; 95% CI: −0.013, −0.002, p = .017). There was no evidence that VRF burden was associated with changes in depressed mood. Discussion Our findings suggest that VRF burden in midlife, but less so in later life, predicts individual differences in depressed mood. These findings are consistent with reports on the importance of midlife VRFs and support the idea that promotion of vascular health in this age group or earlier in life may be critical to maintain mental health across adulthood.