Abstract Background Coronary vasomotor response is different between males and females. However, the prognostic impact of this difference in coronary physiologic indices has not been characterized in patients with no obstructive coronary artery disease (NOCAD). Purpose We aimed to investigate the sex-specific differences of coronary vasomotor function in response to adenosine in a large cohort of patients with NOCAD and its impact on long-term clinical outcomes Methods We included 668 NOCAD patients who underwent invasive coronary vasoreactivity testing using intracoronary incremental doses of adenosine (18–72 μg) with available follow-up data. Indices of coronary vasomotor response were compared between males and females, and their prognostic impact on major adverse cardiovascular events (MACE: death, myocardial infarction, revascularization, and stroke) were analyzed based on sex. Results Females (N=461, mean age 54±12 years) had lower baseline microvascular resistance (BMR) and higher baseline average peak velocity (APV) than males (N=207, mean age 53±13 years), while hyperemic microvascular resistance (HMR) and hyperemic APV were similar between males and females. Consequently, coronary flow reserve (CFR: hyperemic/baseline APV) and resistive reserve ratio (RRR: BMR/HMR) were lower in females than males (Figure 1A). Lower CFR and RRR, as well as lower BMR and higher baseline APV were associated with MACE only in males, but not in females. Higher HMR was the only predictor for MACE in females (Figure 1B). Conclusions Sex-specific differences in coronary vasomotor response to adenosine may provide different prognostic values between males and females. Funding Acknowledgement Type of funding sources: None.