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Introduction: Both trauma exposure and post-traumatic stress disorder (PTSD) are associated with increased risk of cardiovascular disease (CVD), the leading cause of death in the USA. Endothelial dysfunction, a modifiable, early marker of CVD risk, may represent a physiological mechanism underlying this association. This mechanism-focused cohort study aims to investigate the relationship between PTSD (both in terms of diagnosis and underlying symptom dimensions) and endothelial dysfunction in a diverse, community-based sample of adult men and women., Methods and Analysis: Using a cohort design, 160 trauma-exposed participants without a history of CVD are designated to the PTSD group (n=80) or trauma-exposed matched control group (n=80) after a baseline diagnostic interview assessment. Participants in the PTSD group have a current (past month) diagnosis of PTSD, whereas those in the control group have a history of trauma but no current or past psychiatric diagnoses. Endothelial dysfunction is assessed via flow-mediated vasodilation of the brachial artery and circulating levels of endothelial cell-derived microparticles. Two higher order symptom dimensions of PTSD-fear and dysphoria-are measured objectively with a fear conditioning paradigm and attention allocation task, respectively. Autonomic imbalance, inflammation, and oxidative stress are additionally assessed and will be examined as potential pathway variables linking PTSD and its dimensions with endothelial dysfunction. Participants are invited to return for a 2-year follow-up visit to reassess PTSD and its dimensions and endothelial dysfunction in order to investigate longitudinal associations., Ethics and Dissemination: This study is conducted in compliance with the Helsinki Declaration and University of California, Los Angeles Institutional Review Board. The results of this study will be disseminated via articles in peer-reviewed journals and presentations at academic conferences and to community partners., Trial Registration Number: NCT03778307; pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)