Blood pressure (BP) variability is generally considered to be due to neurogenic influences on arterioles modulating peripheral resistance, as well as variations in stroke volume (SV). However, for a given change in peripheral resistance or SV, the degree of BP variability is modulated by the stiffness of large conduit arteries. Recent epidemiological evidence shows that cardiovascular risk is not only related to the average arterial pressure, but also to the degree of diurnal variability. In addition, short-term variability has been shown to be related to aortic stiffness measured as pulse wave velocity, a strong independent predictor of cardiovascular risk. This study addresses the relation between large artery stiffness and BP variability using a lumped parameter model of the systemic circulation described by total arterial compliance, total peripheral resistance (TPR) and aortic characteristic impedance. The variability in TPR is simulated using a random function with a Gaussian distribution and changes in arterial stiffness are simulated by variation in compliance, where compliance is either linear (pressure independent) or nonlinear (pressure dependent). Simulation results show that (i) BP variability is greater when due to changes in TPR compared to similar relative changes in SV, (ii) pressure dependency of arterial stiffness results in a curvilinear relation between systolic BP variability and mean arterial pressure (MAP), such that a critical mean pressure (MAPc) exists for minimal BP variability, (iii) increase in arterial stiffness (as occurs with aging) result in a higher MAPc for minimal BP variability, or increased BP variability at older age for similar values of MAP. These findings suggest that interventions aimed at reducing BP variability will need to consider large artery stiffness for optimal efficacy.