Determine if sex differences in NIRS-based microvascular reperfusion are similarly apparent using the 10-second reactive hyperemia slope of the StO2 signal (slope 2) and the halftime to maximal reperfusion (T 1/2). Healthy, recreationally active males (N = 31) and females (N = 31) between 18-82 years took part in this study. A NIRS VOT was performed on the tibialis anterior muscle and reperfusion was quantified using slope 2 (% s-1) and T 1/2 (seconds). Adipose tissue thickness (ATT) was higher in females (p = 0.009) which was associated with a lower StO2 (p = 0.001) and O2Hb (p = 0.05) signal range. The StO2 slope 2 was significantly steeper in males vs. females (p = 0.001) but not after correcting for ATT (p = 0.295). There were no sex differences in StO2 T 1/2 (p = 0.067) or O2Hb T 1/2 (p = 0.197). In a subset of males (N = 26) and females (N = 21) with similar ATT, there were no sex differences in StO2 slope 2 (p = 0.068), StO2 T 1/2 (p = 0.491), or O2Hb T 1/2 (p = 0.899). An ATT-corrected StO2 slope 2 or the T 1/2 approach is recommended for analysis of NIRS-based microvascular reperfusion when differences in ATT are present between sexes.