Elevated cardiovascular mortality has been shown to be associated with increased arterial stiffness. However, the contribution of tissue accumulation of advanced glycation end products (AGEs) to increased arterial stiffness is unclear. We examined whether skin autofluorescence, a recently developed marker of tissue accumulation of AGEs, is associated with arterial stiffness in 120 Japanese patients with end-stage renal disease (ESRD) and 110 age- and sex-matched control subjects. The ESRD patients had significantly higher pulse wave velocity (PWV), a noninvasive measure of arterial stiffness, and skin autofluorescence than the control subjects. Skin autofluorescence was significantly associated with age in the group of all subjects (Rs = 0.255, Spearman rank correlation test) and that of control subjects (Rs = 0.493), but not in the group of ESRD subjects (Rs = 0.046). The PWV was significantly and positively associated with skin autofluorescence in the group of all subjects (Rs = 0.335), controls (Rs = 0.246), and ESRD subjects (Rs = 0.205). Multiple regression analyses showed that, in the group of all subjects, association of skin autofluorescence with PWV was significant even after adjustment for other covariates including the presence of ESRD and age. Moreover, for ESRD subjects, a significant association between skin autofluorescence and PWV was found, independent of age. Our findings demonstrate the potential usefulness of skin autofluorescence in people of color and demonstrate clinically for the first time the potential involvement of tissue accumulation of AGEs in the pathophysiology of arterial stiffness.