SUMMARYWe discuss the implementation and calibration of a new generalized structured tree boundary condition for hemodynamics. The main idea is to approximate the impedance corresponding to the vessels downstream from a specific outlet. Unlike previous impedance conditions, the one considered here is applicable to general transient flows as opposed to periodic ones only. The physiological character of the approach significantly simplifies calibration. We also describe a novel way to incorporate autoregulation mechanisms in structured arterial trees at minimal computational cost. The strength of the approach is illustrated and validated on several examples through comparison with clinical data. Copyright © 2014 John Wiley & Sons, Ltd.