INTRODUCTION: This study aimed to assess changes in common carotid (CA) and superficial femoral (FA) arterial stiffness during long-duration spaceflight.METHODS: Ultrasound imaging was used to investigate the CA and FA of 10 astronauts preflight (PRE), on flight day 15 (FD15), after 4–5 mo (FD4–5m), and 4 d after return to Earth (R+4). Arterial wall properties were assessed through the calculation of strain, stiffness (β), pressure-strain elastic modulus (Ep), and distensibility (DI). Stiffness indices were assessed for potential correlations to measurements of intima-media thickness (IMT).RESULTS: Significant effects of spaceflight were found for all CA stiffness indices, indicating an increase in arterial stiffness. CA strain was reduced by 34 ± 31% on FD15 and 50 ± 16% on FD4–5m and remained reduced by 42 ± 14% on R+4 with respect to PRE values. On FD4–5m, with respect to PRE values, DI was reduced by 46 ± 25% and β and Ep were increased by 124 ± 95% and 118 ± 92%, respectively. FA arterial stiffness indices appeared to show similar changes; however, a main effect of spaceflight was only found for strain. Correlation analysis showed weak but significant relationships between measurements of CA IMT and arterial stiffness indices, but no relationships were found for FA measurements.DISCUSSION: The observed change in CA and FA stiffness indices suggest that spaceflight results in an increase in arterial stiffness. That these changes were not strongly related to measurements of IMT suggests the possibility of different mechanisms contributing to the observed results.Arbeille P, Provost R, Zuj K. Carotid and femoral arterial wall distensibility during long-duration spaceflight. Aerosp Med Hum Perform. 2017; 88(10):924–930.