Abstract Background An aortic dissection is the most devastating complication of thoracic aortic disease. Several non- and syndromic conditions such as a bicuspid aortic valve (BAV) and Marfan syndrome (MFS) have a severely increased risk to develop a thoracic aortic aneurysm and dissection. To date, the medial layer has been extensively studied in search of the pathogenetic mechanisms leading to aortic complications. Objective We aim to determine whether intimal layer pathology is characteristic in all thoracic aortopathy regardless of the underlying etiology. Method A total of 176 aortic wall specimen were studied for the intimal layer architecture including the intimal thickness, endothelial cell morphology, and atherosclerosis. Specimens were derived from four patient groups: BAV (n = 70, age 57 ± 8.9 years), isolated tricuspid aortic valve (TAV) (n = 38, age 64.9 ± 11.0 years), MFS with a TAV (n = 8, age 34.2 ± 11.0 years), type A dissections with a TAV (n = 60, age 62.7 ± 10 years). Results The intimal layer is significantly thinner in BAV, MFS, and type A aortic dissection as compared to the isolated TAV patients (p < 0.001). Intimal atherosclerosis was also significantly less present in the three groups as compared to the isolated TAV (p < 0.05). Discussion A thin intimal layer is a common finding in the thoracic aortopathy patients. Studies aiming at preventing future aortic complications should focus on the intimal pathology as a common effector pathway in thoracic aortopathy.