Introduction: Cardiovascular disease (CVD) remains the leading cause of death for females in the United States. Although premenopausal females are typically thought to be protected from CVD, available data supports growing CVD risk in females before menopause by virtue of PTSD. Arterial stiffness is a well-known risk factor for CVD and estradiol (E2) in premenopausal females is known to promote good vascular function. Therefore, the purpose of the present study was to investigate the effects of E2 on arterial compliance in young trauma-exposed females with and without a PTSD diagnosis. We hypothesized that E2 levels will be negatively associated with arterial stiffness in women with PTSD. Methods: Sixty-eight trauma-exposed females (27 ± 7.4 years, 26.5 ± 5 kg/m2) from diverse backgrounds with (PTSD+, n=37) and without (PTSD-, n=31) a diagnosis of PTSD were included in this analysis. We collected blood samples to quantify plasma estrogen (E2) levels and assessed pulse wave velocity (PWV) using applanation tonometry. PWV is a non-invasive technique used to measure the speed at which blood travels from the aorta to the femoral artery using a tonometer that is placed over the carotid artery while a blood pressure cuff is placed over the femoral artery. PTSD symptom severity was assessed using the PTSD checklist for DSM 5 and blood samples were analyzed for total E2 using the quantitative sandwich enzyme immunoassay technique (ELISA). We used Pearson correlations and multiple linear regression to determine associations between E2 and PWV in the entire sample and in each group. Given our previous findings on sleep effciency and vascular function, we controlled for sleep effciency in the current analysis. Sleep effciency was objectively measured as the relative time (%) spent asleep while in bed, using wrist actigraphy for seven days. Results: Our analysis revealed an overall weak correlation between E2 and PWV (r=-0.028, p=0.024). However, when we examined each group, we found no association between E2 levels and PWV (r=-0.01, p=0.95) in the PTSD+ group. In contrast, in the PTSD- group, we found a strong association between E2 levels and PWV (r=-0.51, p=0.004). Furthermore, we conducted a multiple linear regression in the PTSD- group to detect the predictive value of E2 levels on PWV, controlling for sleep effciency, age, BMI, blood pressure, and PCL5. The model was significant (R2=0.65, adjusted R2=0.56, p<0.001) with estradiol (β=-0.24, p=0.005) and diastolic blood pressure (β=-0.059, p<0.001) as the strongest predictors. Thus, for every unit increase in E2 level, PWV decreased by 0.24 in the PTSD- group. Conclusion: Our analysis revealed that although E2 levels were negatively associated with PWV in young trauma-exposed females without PTSD, it was not the case in those with a PTSD diagnosis. These findings suggest that PTSD disrupts the association between E2 and arterial compliance in young females. K01HL161027 and UMN CTSI UL1TR002494 no disclosure. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.