Background: Carotid-to-femoral pulse wave velocity (c-f PWV) is commonly used to assess large artery stiffness, particularly as a surrogate of aortic stiffness. Given that c-f PWV represents the average stiffness of all main arteries along the carotid-to-femoral arterial pathway, without specifically accounting for the stiffness of the proximal aorta, we hypothesized that c-f PWV may not represent stricto sensu the stiffness of the ascending aorta (AAO), which is the main contributor to total arterial compliance (C T). Methods: To test our hypothesis, we recruited 45 healthy volunteers from different age groups. We evaluated the relation between c-f PWV and different indices of proximal aorta stiffness calculated from distensibility (AAOdist PWV) and characteristic impedance (Z c) in frequency (AAO Zc(f) PWV) and time domain (AAOZc(t) PWV) and compared their relationships with age and C T. 2D phase contrast MRI was performed to measure AAO flow and cross-sectional area. Tonometry was used to obtain c-f PWV and pressure waveforms. Results: In healthy individuals, AAO PWV indices demonstrated a strong relationship with each other (R ≥ 0.86), but c-f PWV did not show high correlations with AAO PWV indices (R ≤ 0.50). All AAO PWV indices increased with age (P ≤ 0.05); however, c-f PWV did not increase from young to middle-aged (P = 0.13) and middle-aged to old age groups (P = 0.28). AAO PWV indices correlated well with CT (R 2 ≥ 0.60), whereas c-f PWV did not (R 2 = 0.23). Conclusion: The present study reveals that a complete understanding of large artery stiffness requires the direct assessment of proximal aortic stiffness rather than surrogate indices such as c-f PWV.