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The microvascular resistance reserve (MRR) is an innovative index to assess the vasodilatory capacity of the coronary circulation while accounting for the presence of concomitant epicardial disease. The MRR has shown to be a valuable diagnostic and prognostic tool in the general coronary artery disease (CAD) population. However, considering the fundamental aspects of its assessment and the unique hemodynamic characteristics of women, it is crucial to provide additional considerations for evaluating the MRR specifically in women. The aim of this study was to assess the diagnostic and prognostic applicability of the MRR in women and assess the potential differences across different sexes. From the ILIAS Registry, we enrolled all patients with a stable indication for invasive coronary angiography, ensuring complete physiological and follow-up data. We analyzed the diagnostic value by comparing differences between sexes and evaluated the prognostic value of the MRR specifically in women, comparing it to that in men. A total of 1494 patients were included of which 26% were women. The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47–0.96, p = 0.027) and men (HR 0.84, 0.74–0.95, p = 0.007). The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. An abnormal MRR similarly predicted MACE at 5-year follow-up in both women and men. The MRR seems to be equally applicable in both women and men with stable coronary artery disease. • The correlation between MRR and CFR was good and similar between women (r = 0.80, p < 0.005) and men (r = 0.81, p < 0.005). • The MRR was an independent and important predictor of MACE in both women (HR 0.67, 0.47–0.96, p = 0.027) and men (HR 0.84, 0.74–0.95, p = 0.007). • The optimal cut-off value for MRR in women was 2.8 and 3.2 in men. • The MRR seems to be equally applicable in both women and men with stable coronary artery disease. [ABSTRACT FROM AUTHOR]