Background: We hypothesized that a reversal of the physiological stiffness gradient, previously reported in end-stage renal disease, begins in the early stages of chronic kidney disease (CKD) and that chronic inflammation produces a different arterial phenotype in patients with ulcerative colitis (UC). Objectives: To assess the extent of arterial stiffening in the central (carotid-femoral pulse wave velocity, cf.-PWV) and peripheral arteries (carotid-radial pulse wave velocity, cr-PWV) and to explore the determinants of the stiffness gradient in UC and in CKD. Methods: We enrolled 45 patients with UC, 45 patients with stage 3-4 CKD and 45 matched controls. Results: Despite the comparable cf.-PWV, the cr-PWV was higher in patients with UC than in those with CKD (median: 8.7 vs. 7.5. m/s; p <. 0.001) and, consequently, the PWV ratio was lower (median: 0.97 vs. 1.12; p <. 0.001). In patients with CKD a stiffness mismatch was reported starting from stage 3B. The PWV ratio was associated with age and C-reactive protein (beta: 0.08 z-score, 95%CI 0.02-0.14; p = 0.01) or active disease (beta: 0.43 z-score, 95%CI 0.003-0.857; p = 0.048) in patients with UC and with age and glomerular filtration rate (beta: -0.56 z-score, 95%CI -1.05 to -0.07; p = 0.02) in patients with CKD. Conclusions: The arterial phenotype differed between UC and CKD. The reversal of the arterial stiffness gradient is evident in CKD patients starting from stage 3B but not in patients with UC and comparable cf.-PWV. In patients with UC, the stiffness of both elastic and muscular arteries is increased as a consequence of inflammation.