What is the central question of this study? Can near-infrared spectroscopy (NIRS)-derived post-occlusion tissue oxygen saturation recovery kinetics be used to study age-related impairments in microvascular function? What is the main finding and its importance? Using a previously established 5min cuff occlusion protocol, we found that NIRS-derived indices of microvascular function were markedly reduced in elderly compared with young participants. However, when we controlled for the absolute level of vasodilatory stimulus and matched the tissue desaturation level between groups, we found similar responses in young and elderly participants. Overall, these data highlight the important role NIRS can serve in clinical vascular biology, but also establishthe need for assessing tissue ischaemiaduring cuff occlusion protocols. Near-infrared spectroscopy (NIRS) has emerged as a promising tool to evaluate vascular reactivity invivo. Whether this approachcan be used to assess age-related impairments in microvascular function has not been tested. Tissue oxygen saturation (StO2) post-occlusion recovery kinetics were measured in two distinct age groups (<35 and >65years of age) using NIRS placed over the flexor digitorum profundus. Key end-points included the following: (i)the desaturation rate during cuff occlusion; (ii)the lowest StO2 value obtained during ischaemia (StO2min); (iii)StO2 reperfusion rate; (iv)the highest StO2 value reached after cuff release (StO2max); and (v)the reactive hyperaemia area under the curve (AUC). At first, using a conventional 5min cuff occlusion protocol, the elderly participants achieved a much slower rate of oxygen recovery (1.5±0.2 versus 2.5±0.2%s-1 ), lower StO2max (85.2±2.9 versus 92.3±1.5%) and lower reactive hyperaemia AUC (2651.8±307.0 versus 4940.0±375.8%s-1 ). However, owing to a lower skeletal muscle resting metabolic rate, StO2min was also significantly attenuated in the elderly participants compared with the young control subjects (55.7±3.5 versus 41.0±3.4%), resulting in a much lower ischaemic stimulus. To account for this important difference between groups, we then matched the level of tissue ischaemia in a subset of young healthy participants by reducing the cuff occlusion protocol to 3min. Remarkably, when we controlled for tissue ischaemia, we observed no differences in any of the hyperaemic end-points between the young and elderly participants. These data highlight the important role NIRS can serve in vascular biology, but also establish the need for assessing tissue ischaemia during cuff occlusion protocols.