The Fontan circulation is associated with an increased central venous pressure, decreased ventricular preload, and increased afterload. We postulated that these central hemodynamic abnormalities would have consequences for the structural and functional properties of the peripheral arteries and veins, and performed a cross-sectional study in a tertiary health-care setting. We prospectively examined venous and arterial wall morphology by very high resolution ultrasound (VHRU, 25–55 MHz), and function by conventional vascular ultrasound (flow-mediated dilatation, FMD) and applanation tonometry (pulse wave velocity, PWV) in 28 patients after the Fontan procedure (age 14.8 ± 1.3 years) and 54 age-matched controls. Pig venous samples were studied with VHRU and compared with histology for accuracy. The precision of the venous VHRU method was studied in healthy volunteers. The lumen dimension was reduced in Fontans compared with controls in the common carotid, brachial, radial, and femoral arteries (p < 0.05). The common carotid, brachial, radial, ulnar, femoral, and dorsal tibial artery intima-media thicknesses (IMTs) and the brachial, ulnar, and femoral artery adventitial thicknesses were decreased (p < 0.05 for all), while the cubital and dorsal tibial vein IMTs were increased in Fontans (p < 0.001). FMD, abdominal aortic stiffness, and carotid-femoral PWV were similar, while carotid-radial artery PWV was increased in Fontans (p < 0.01). Venous wall layer assessment with VHRU was accurate and precise. The Fontan circulation is associated with significant arterial and venous remodeling, presumably reflecting abnormalities of central hemodynamics. These novel data may be of clinical importance in the circulatory management as well as the understanding of the early pathogenesis of vasculopathy in patients after the Fontan procedure.