Objective: This study aimed at validating photoplethysmography for assessing bilateral blood pressure differences through investigating the correlations of digital volume pulse with arteriosclerosis risk. Methods: Totally, 111 subjects (70 healthy and 41 diabetic) were recruited. Demographic, blood pressure and anthropometric data were recorded. Blood was collected for determining serum cholesterol, total triglyceride, total cholesterol, high-/low-density lipoprotein cholesterol, fasting blood sugar and glycated haemoglobin concentrations. Arterial stiffness was assessed with electrocardiogram-based pulse wave velocity, crest time and inter-digital volume pulse differences. Results: Receiver operating characteristic curve demonstrated high inter-digital volume pulse difference sensitivity to glycated haemoglobin level over 6.5%. Linear regression analysis demonstrated significant correlation between inter-digital volume pulse difference and electrocardiogram-based pulse wave velocity (r=0.692, p<0.001). Compared with electrocardiogram-based pulse wave velocity, inter-digital volume pulse difference exhibited highly significant correlations with age, glycated haemoglobin level, pulse pressure, total cholesterol/high-density lipoprotein ratio, crest time, high-density lipoprotein and systolic blood pressure (all ps<0.001). Conclusion: In conclusion, the results not only demonstrated successful application of a novel non-invasive waveform contour index, inter-digital volume pulse difference, in differentiating young from aged subjects and patients with good diabetic control from those with poor diabetic control but also validated its use in identifying arteriosclerosis risks. The results, therefore, endorse its domestic application as non-invasive tool for arteriosclerosis risk screening.