OBJECTIVE : The aim of the present study was to investigate why the magnitude of reactive hyperemia (RH) observed by pulse volume amplitude (PVA) after arm occlusion differs greatly among study subjects. METHODS : Healthy subjects (n = 12) in the age range of 22-30 years participated in this study. Vascular reactivity was assessed by measuring the changes in finger PVA simultaneously in the test (occluded arm) and control arm (contralateral non-occluded arm) using two separate Photoplethysmographic sensors. Short-term HRV was computed from simultaneously acquired lead II ECG signal to monitor the changes in cardiac sympathetic nervous activity. RESULTS : The observed coefficient of variation for inter-subject variability in PVA response in test arm during second minute of RH was 115.3%. In the control arm, significantly reduced PVA was observed during the period of occlusion as well as RH. This observation was corroborated by simultaneously acquired short-term HRV which showed a significant rise in total power (p value < 0.005) and low-frequency (LF) power (p value < 0.05) during release of occlusion when compared to the baseline. A significant positive correlation (Spearman r = 0.33; p = 0.02) was observed between % change in PVA in the control arm and in the test arm for first 3 min of RH. CONCLUSIONS : Sympathetic activation possibly plays an important role in mediating the inter-subject variability of vascular responses during reactive hyperemia which warrants simultaneous recording of both the test and the control arm responses during RH to accurately assess endothelial function.