Objectives: We examined the hypothesis that a stiff aorta is associated with reduced coronary blood flow (CBF) and CBF response to percutaneous coronary intervention (PCI). Background: Aortic mechanical properties are thought to affect CBF, with increased stiffness associated with decreased coronary perfusion. Animal studies are conflicting and human evidence lacking. Even less is known about the effects of aortic stiffness on CBF response to successful PCI. Method: In 18 subjects undergoing elective PCI, a Doppler velocity guide wire was positioned proximal to a severe coronary stenosis to measure resting and adenosine-induced hyperaemic CBF before and after PCI. Stenosis severity was assessed with Doppler velocity and pressure guidewires. Aortic mechanical indices measured included central pulse wave velocity (cPWV) and central pulse pressure (cPP). Results: PCI was successful in all subjects (diameter stenosis: 88±9 to 2±7%; coronary flow velocity reserve: 1.8±0.6 to 3.0±0.8; fractional flow reserve: 0.57±0.19 to 0.92±0.06; all P<0.001). Adjusting for age and gender, resting and hyperaemic CBF were inversely related to cPWV irrespective of the presence of stenosis (resting: before PCI- r²=0.452, P<0.01; after PCI- r²=0.261, P=0.043; hyperaemic: before PCI- r²=0.503, P=0.005; after PCI- r²=0.500, P=0.002), whilst they were related to cPP in absence of stenosis (resting: r²=0.368, P=0.022; hyperaemic: r²=0.370, P=0.016). Hyperaemic CBF response (P=0.005) and hyperaemic CBF improvement from PCI (P=0.025) were less marked in a stiff than compliant aorta. Conclusions: A stiff aorta is associated with a reduction in CBF, a lower hyperaemic CBF response and may reduce the improvement in hyperaemic CBF after successful PCI.