Abstract Background Hypercortisolism due to Cushing's Disease (CD), Ectopic ACTH Syndrome (EAS), adrenal adenoma (AA), or Cyclical Cushing's Syndrome (cCS) is associated with increased cardiovascular morbidity and mortality. The mechanism(s) by which hypercortisolism increases coronary artery atherosclerosis is not understood. We previously used Multidetector computerized tomographic coronary angiography (MDCT) to demonstrate significantly increased noncalcified plaque volume in CS patients. Time-Resolved Phase-Sensitive Dual Inversion Recovery technique (TRAPD-3T) magnetic resonance imaging (MRI) is a recently developed noninvasive tool to examine vessel wall thickness (VWT) of coronary arteries. We postulated that TRAPD MRI might be used as an independent biomarker of coronary artery disease burden in CS. Methods 29 CS patients (AA: 1, CD: 14, EAS: 12, cCS: 2) and 29 age, gender, BMI and Framingham score-matched control patients (CPts) underwent TRAPD-3T MRI of the proximal right coronary artery vessel wall thickness. Prior to MRI, 25 CS patients were untreated and 3 were treated. Vessel wall thickness was measured as the average distance between inner and outer boundaries of the vessel wall. Vessel wall thickness variation was calculated as the standard deviation of these measurements. Circularity was the ratio of the mean thickness over the variation in measurement. The larger the circularity ratio, the more consistent the vessel wall thickness and the less eccentric the blood vessel. All measurements given as mean ± SD. Paired t-tests were used to compare the groups. Results Compared to control subjects, CS patients had significantly higher values for coronary VWT (CS: 1.38 ± 0.19mm, CPts: 1.27 ± 0.15mm; p < 0.015) and VWT variation (CS: 0.19 ± 0.072mm, CPts: 0.14 ± 0.045mm; p <0.002). By contrast, control patients had significantly higher vessel wall circularity compared to CS patients (CS: 9.58 ± 2.65mm, CPts: 8.05 ± 2.65mm; p<0.03). CS pts had less vessel wall circularity, thus increased eccentricity, indicating more advanced atherosclerosis. The degree of hypercortisolism was not associated with Framingham risk score, VWT, variability, or circularity. There was also no significant difference in VWT, variability, or circularity between males and females with hypercortisolism. Conclusion The finding of more advanced atherosclerosis in CS patients compared to age-matched controls suggests that excess cortisol may directly or indirectly promote atherosclerotic plaque formation. Adequate treatment of cardiovascular risk factors along with treatment of underlying hypercortisolism is essential to reducing morbidity and mortality. The TRAPD MR technique has promise as a non-invasive and radiation-free technique to monitor CAD and its prevention/treatment in these patients during and after treatment. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.