Men exhibit greater values of reactive hyperemia than women even when controlling for the magnitude of desaturation during transient ischemia. Factors other than the ischemic vasodilatory stimulus, such as skeletal muscle mass and quality, likely provoke the commonly reported sex differences in reactive hyperemia measured by near-infrared spectroscopy. , Men and women exhibit different near-infrared spectroscopy (NIRS) outcomes in response to vascular occlusion tests (VOT), which may be due to phenotypic characteristics or different degrees of desaturation during ischemia. The minimum skeletal muscle tissue oxygenation (StO 2min ) observed during a VOT may be the primary determinant of reactive hyperemic (RH) responses. Our purpose was to determine the contribution StO 2min and participant characteristics including adipose tissue thickness (ATT), lean body mass (LBM), muscular strength, and limb circumference to NIRS-derived indexes of RH. Also, we aimed to determine if matching StO 2min would eliminate NIRS-VOT sex differences. Thirty-one young adults completed one or two VOTs during which the vastus lateralis was continuously assessed for StO 2 . The men and women each completed a standard VOT with a 5-min ischemic phase. The men completed a second VOT with a shortened ischemic phase to produce a matching StO 2min to the minimum of the women observed during the standard VOT. Mean sex differences were determined with t tests, and relative contributions were assessed with multiple regression and model comparison approaches. During the 5-min ischemic phase, the men exhibited greater upslopes (1.97 ± 0.66 vs. 1.23 ± 0.59%·s −1 ) and greater StO 2max than the women (80.3 ± 4.17 vs. 76.2 ± 2.86%). Analysis revealed StO 2min was a greater contributor to upslope than sex and/or ATT. For StO 2max , sex was the only significant predictor ( r 2 = 0.26, men ∼4.09% textgreater women). Experimentally matching StO 2min did not eliminate the sex differences in upslope or StO 2max , suggesting that characteristics other than the degree of desaturation primarily provoke sex differences in RH. NEW & NOTEWORTHY Men exhibit greater values of reactive hyperemia than women even when controlling for the magnitude of desaturation during transient ischemia. Factors other than the ischemic vasodilatory stimulus, such as skeletal muscle mass and quality, likely provoke the commonly reported sex differences in reactive hyperemia measured by near-infrared spectroscopy.