Movement to upright posture may result in marked drop of blood pressure with susceptibility to injury from syncope and falls in patients with orthostatic hypotension. The purpose of this study was to determine if increasing negative intrathoracic pressure by using an inspiratory impedance threshold device before change of posture diminishes blood pressure fall by enhancing venous return. Eighteen healthy subjects and 22 orthostatic hypotension patients were randomized to either an active (impedance 7 cmH2O) or sham (no inspiratory impedance) impedance threshold device. Arterial blood pressure, heart rate, and estimated stroke volume and total peripheral resistance were recorded in the supine and upright postures using a noninvasive finger arterial blood pressure monitor. After a rest period, the alternate impedance threshold device (sham or active) was tested in each individual. Compared with the sham impedance threshold device test, the active impedance threshold device resulted in significant reduction in the magnitude of upright posture-induced fall in blood pressure and a greater increase of total peripheral resistance after standing in both healthy subjects and orthostatic hypotension patients. Stroke volume was not measurably altered. Among all subjects who exhibited a postural blood pressure drop >10 mmHg on the day of study, active impedance threshold device treatment consistently blunted blood pressure fall during the initial 100 seconds after standing (<0.04). Induced orthostatic symptoms were less severe with the active impedance threshold device both at onset of upright posture and during 30 seconds of standing. Enhancing impedance to inspiration may prove useful as adjunctive therapy for diminishing symptoms associated with movement to upright posture in individuals with orthostatic hypotension.