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Background: The effect of upright posture on the level of augmentation index (AIx) remains controversial [1–3]. Phenotypic differences in AIx responses to upright posture are unknown. Methods: Altogether 323 women and 315 men without cardiovascular disease and medications with direct cardiovascular influences were subjected to passive head-up tilt (5-min supine, 5-min upright). Haemodynamics were recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Results: Mean (SD) age was 45.6 (1.2) years, BMI 26.8 (4.4) kg/m2, and average blood count, plasma lipids and creatinine were normal. AIx decreased from supine 22.7% (11.9) to upright 13.8% (12.2) (p < 0.001), while heart rate related AIx@75 decreased from 17.9% (11.8) to 13.9% (11.0) (p < 0.001), respectively. In stepwise linear regression analyses, the explanatory variables for upright reduction in AIx were changes in ejection duration (β = 0.744), aortic reflection time (β = −0.491), and stroke volume (β = 0.117); and supine ejection duration (β=0.312), systemic vascular resistance (SVR) (β = −0.271), pulse wave velocity (PWV) (β = −0.203), and systolic blood pressure (β=0.081) (p≤0.001 for all). When divided to quartiles according to the supine-to-upright change in AIx 1) the quartile with lowest supine AIx had highest upright AIx, lowest supine SVR and PWV, and lowest upright heart rate; 2) the quartile with highest supine AIx had lowest upright AIx, highest supine SVR and PWV, and highest upright heart rate. Conclusions: The level of AIx is decreased in the upright position. The phenotypic differences in the supine-to-upright change in AIx may explain why this variable has not predicted cardiovascular events in all endpoint studies.