Postprandial metabolic imbalances are important indicators of later developing cardiovascular disease (CVD). This study investigated the effects of food anthocyanins on vascular and microvascular function, and CVD associated biomarkers following a high fat high energy (HFHE) meal challenge in overweight older adults. Sixteen subjects (13 female, 3 male, mean age 65.9 SD 6.0 and body mass index 30.6kg/m2 SD 3.9) participated in a crossover, randomized, controlled, double-blind clinical trial (registered under Australian New Zealand Clinical Trials Registry, identifier no. ACTRN12620000437965). Participants consumed a HFHE meal with a 250mL dose of either intervention (anthocyanins-rich Queen Garnet Plum) or control (apricot) juice. Blood samples and blood pressure measures were collected at baseline, 2h and 4h following the HFHE meal. Vascular and microvascular function were evaluated at baseline and 2h after the HFHE meal. Participants had a higher 2h postprandial flow-mediated dilatation (+1.14%) and a higher microvascular post-occlusive reactive hyperaemia (+0.10 perfusion units per mmHg) when allocated to the anthocyanin compared to the control arm (P=0.019 and P=0.049, respectively). C-reactive protein was lower 4h postprandially in the anthocyanins (1.80mg/L, IQR 0.90) vs control arm (2.30mg/L, IQR 1.95) (P=0.026), accompanied by a trend for lower concentrations of interleukin-6 (P=0.075). No significant postprandial differences were observed between treatments for blood pressure, triacylglycerol, total cholesterol, serum derivatives of reactive oxidative metabolites, tumor necrosis factor alpha, interleukin-1 beta, or maximum microvascular perfusion following iontophoresis of acetylcholine. Fruit-based anthocyanins attenuated the potential postprandial detrimental effects of a HFHE challenge on parameters of vascular and microvascular function, and inflammatory biomarkers in overweight older adults. Anthocyanins may reduce cardiovascular risk associated with endothelial dysfunction and inflammatory responses to a typical high fat 'Western' meal. Further studies are required to better elucidate the clinical implications of postprandial biomarkers of CVD.