Arterial diameters at branch points are believed to conform to design principles that optimize circulatory efficiency and maintain constant shear stress across arterial networks. The objective of this study was to examine whether optimality at bifurcations is affected in individuals with atherosclerosis. Retinal images were analysed in normotensive men with abnormal ankle brachial index (n=13) and healthy controls (n=8), matched for age and clinic blood pressure. Compared with controls, men with peripheral vascular disease had adverse metabolic profiles (relative insulin resistance and greater total cholesterol levels). In healthy men, retinal arterial diameters at bifurcations conformed to predicted optimal values but in men with peripheral vascular disease, junction exponents deviated significantly from the optimum. Retinal arteriolar bifurcation angles did not differ significantly between the groups. Atherosclerosis is associated with abnormalities in the arteriolar network of the retina. In view of the importance of the endothelium in maintaining network co-ordination of branch diameters this is suggestive of a generalized abnormality of endothelial function in atherosclerosis.