Objective: To assess the time course of adaptations in leg vascular dimension and function within the first 6 weeks after a spinal cord injury (SCI).Design: Longitudinal study design. Setting: University medical center and rehabilitation clinic. Participants: Six men were studied serially at 1, 2, 3, 4, and 6 weeks after SCI.Interventions: Not applicable. Main Outcome Measures: Diameter, blood flow, and shear rate levels of the common femoral artery (CFA), superficial femoral artery (SFA), brachial artery, and carotid artery were measured with echo Doppler ultrasound (diameter, blood flow, shear rate). Endothelial function in the SFA was measured with flow-mediated dilation (FMD). In addition, leg volume and blood pressure measurements were performed.Results: Femoral artery diameter (CFA, 25%; SFA, 16%; PϽ.01) and leg volume (22%, PϽ.01) decreased simultaneously, and these reductions were largely accomplished within 3 weeks postinjury. Significant increases were observed for basal shear rate levels (64% increase at week 3; 117% increase at week 6; PϽ.01), absolute FMD responses (8% increase at week 3, 23% increase at week 6; PϽ.05) and relative FMD responses (26% increase at week 3, 44% increase at week 6; PϽ.001).Conclusions: Our findings show a rapid onset of adaptations in arterial dimension and function to extreme inactivity in humans. Vascular adaptations include extensive reductions in femoral diameter and leg volume, as well as increased basal shear rate levels and FMD responses, which all appear to be largely accomplished within 3 weeks after an SCI.