Early detection of pathological changes in the vasculature is required to identify individuals at risk of cardiovascular diseases. Noninvasive measurement of the second derivative of photoplethysmogram (SDPTG) might aid in evaluating vascular aging. Here we clarified the diagnostic significance of four SDPTG indices for end-organ damage. A total of 1613 community residents (65±10 years) were enrolled. Changes in blood flow volume at the forefinger were measured by photoplethysmography. SDPTG was computationally calculated from the plethysmogram, and the height of five peaks (a-e) on the SDPTG was measured. Carotid intima-media thickness (IMT), brachial-to-ankle pulse wave velocity (baPWV) and silent cerebral lesions were used as indices of end-organ damage. Multivariate analysis identified age, sex, systolic blood pressure and heart rate as strong determinants for the evaluated SDPTG indices, namely b/a, d/a and aging index ([b-d-c-e]/a). In addition, poor glycemic control and carotid IMT were also weakly associated with the SDPTG indices. Compared with other established risk factors, however, the association between the SDPTG indices and carotid IMT was weak or insignificant (b/a: β=0.069, P=0.002; d/a: β=-0.009, P=0.669; and aging index: β=0.047, P=0.037). Further, no significant association was noted between the SDPTG indices and silent lacunar infarction (b/a: P=0.111; d/a: P=0.263; and aging index: P=0.167) and periventricular hyperintensity (b/a: P=0.587; d/a: P=0.254; and aging index: P=0.429). Although the SDPTG indices evaluated here might represent structural and functional changes in arteries, they exhibited limited diagnostic significance for pathophysiological changes in large arteries, as well as small vessel diseases of the brain.