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Background: Acute vasoreactivity testing (AVT) which reflects the compliance of the pulmonary vascular bed has been proven to be of prognostic value. The purpose of the present study is to explore the sex differences of hemodynamics during the AVT and their impact on event‐free survival in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Eighty‐six patients underwent a right heart catheterization and AVT at Shanghai Pulmonary Hospital from February 2009 to February 2018. Univariate and multiple stepwise regression analysis were performed to determine the predictors of independent event‐free survival, and receiver operating characteristic curve was plotted to determine the cut‐off value of independent parameters in CTEPH. Results: There were no significant differences in both demographics and hemodynamics between male and female patients with CTEPH. Except ΔPVR/PVR showed a significantly higher difference in female than male patients (P = 0.034). Male patients had higher mRAP of pre‐ and post‐AVT than female patients in the event‐free subgroup, while, female patients showed higher PVR of pre‐AVT than male patients in the event subgroup (P < 0.05). The mRAP and SvO2 were independent predictors of event‐free survival in female patients both before and after the AVT, whereas ΔSvO2 was an independent predictor of event‐free survival in male patients. Conclusion: Hemodynamics during the AVT varied between male and female patients with CTEPH. Both sexes displayed unique hemodynamic responses that were independently able to predict event‐free survival. Therefore, better estimates of prognosis in CTEPH can be made when sex differences are also taken into consideration. [ABSTRACT FROM AUTHOR]