Peripheral arterial disease (PAD) is a progressive cardiovascular disorder caused by atherosclerosis and is estimated to affect >200 million people globally. The metabolic syndrome has a very strong association with PAD, that is when one form of CVD is present, there is a high possible occurrence of associated CVD events most predominantly obesity. Omega-3 polyunsaturated fatty acids have been associated with benefit for cardiovascular (CV) disease prevention; however, subsequent large-scale randomised-controlled clinical trials have showed variable effects. With our studies showing high-dose EPA in restoring tissue blood flow and oxygenation in ischemic events; successfully understanding its mechanisms is important in its potential manipulation as an adjunct metabolic therapeutic agent. Human umbilical vein endothelial cells were treated with either EPA or DHA (0.0001, 0.001 and 0.01 mg/ml) or both (at 0.01 mg/ml) and angiogenesis was measured using scratch wound (every 2 hours for 8 hours) and tubule formation (after 16 hours) assays. In mice, hind limb ischemia was performed by ligation of the femoral vascular bed. Limb perfusion was measured using laser speckle contrast imaging over two weeks post-ischemia and analysed relative to the contralateral control limb. Mice were treated daily with high-dose EPA or DHA (600 mg/kg/day, oral). EPA treatment resulted in accelerated reperfusion rate at a ratio of 1.0 vs. 9.7 at day 14; P=0.04 but had no effect on angiogenesis in vitro. These data provide important insights to further establish the role of EPA in vascular remodelling, further investigations have been undertaken to understand the influence of omega-3 fatty acids on plaque stability in a tandem stenosis ApoE-/- mouse model with results pending. This data has implications for the use of omega-3 fatty acids as a pharmacological approach for CV prevention adjunct with the metabolic syndrome.