jats:titleAbstract</jats:title>jats:pCentral Pulse Pressure (CPP) and Aortic Pulse Wave Velocity (aPWV) share a positive relationship with cerebral pulsatility and are associated with cerebrovascular disorders including stroke. Our aim was to examine the influence of Augmentation Index (AIx) upon this relationship, first by using a cross sectional design across a wide range of CPP and aPWV in healthy individuals and second, following administration of Glyceryl Trinitrate (GTN) to acutely change AIx. We measured CPP, aPWV, AIx and Middle Cerebral Artery Pulsatility Index (MCAPI) in 99 healthy individuals (54 females). In all individuals, after accounting for the effect of age and gender, MCAPI shared an independent inverse relationship with AIx (jats:italicβ</jats:italic> = −0.515, jats:italicR</jats:italic>jats:sup2</jats:sup> = 0.109; jats:italicp</jats:italic> = 0.001), and a positive relationship with CPP (jats:italicβ</jats:italic> = 0.570, jats:italicR</jats:italic>jats:sup2</jats:sup> = 0.093; jats:italicp</jats:italic> = 0.003) but not aPWV (jats:italicp</jats:italic> > 0.05). GTN was administered to 25 of these participants (14 females). Following GTN, AIx75 decreased in all participants relative to baseline (12 ± 19 to 5 ± 16%; jats:italicp</jats:italic> = 0.0001). In the 20 min following GTN administration, CPP shared a positive relationship with MCAPI (jats:italicβ</jats:italic> = 0.305, jats:italicR</jats:italic>jats:sup2</jats:sup> = 0.042; jats:italicp</jats:italic> = 0.002) while AIx, adjusted for heart rate (AIx75), shared an inverse relationship with MCAPI (jats:italicβ</jats:italic> = −0.320, jats:italicR</jats:italic>jats:sup2</jats:sup> = 0.019; jats:italicp</jats:italic> = 0.031). These findings indicate that the positive relationship between CPP and MCAPI may be somewhat modified by AIx. This suggests that an increased AIx may weakly attenuate increases in MCAPI that are associated with aortic stiffening in a healthy population at rest, but also following acute reductions in AIx75 after administration of GTN.</jats:p>