There is growing evidence to suggest that vascular disease plays an important role in late life depressive disorder. The aim of this study was to characterize vascular impairment in late life depression. Assessment of endothelial function, arterial stiffness, and atherosclerosis in a variety of vessel beds was carried out in 25 subjects with late life depression and 21 nondepressed control subjects. All study subjects underwent wave velocity, pulse wave analysis, carotid intima media thickness analysis, and magnetic resonance imaging of the brain and a subset gluteal fat biopsy and direct assessment of small artery endothelial function. There were no baseline differences in demographics or a range of vascular risk factors between the groups. There was a generalised vascular dysfunction in depressed subjects with significantly more atherosclerosis, poorer endothelial function and increased arterial stiffness. On neuroimaging, depressed subjects had significantly more dilated Virchow-Robin spaces in the basal ganglia. White matter lesion volumes in all regions were higher in depressed subjects but not significantly so. Furthermore, subjects with late onset depression (onset >60years) had greater vascular impairment when compared to those with early onset illness. Lastly, depressed subjects who did not respond to antidepressant monotherapy showed more vascular dysfunction compared to responders. The study has a number of limitations including the small sample size and as the study was cross sectional, the observed relationship between vascular dysfunction and depression is associative rather than causal. Further research in larger samples is required to address the methodological limitations of this study. If the study results are confirmed, the use of vasoprotective drugs to improve vascular function or retard atherosclerosis as diasease modifying agents in late life depression would be a rational development.