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There is growing evidence of a differential etiological basis for thoracic aortic aneurysms (TAA), with ascending (As) TAAs being genetically mediated and descending (Des) TAAs more strongly related to acquired pathologies. A comprehensive literature review of this hypothesis has not been carried out. We carried out a systematic literature review based on the latest guidelines on TAA endorsed by the American Heart Association. The etiologies were classified as genetic and inherited, the studies were tabulated accordingly, and Hill’s epidemiological criteria of causality were applied. We found 38 studies addressing the etiology of TAAs. Out of these, 17 were about genetic causes, 9 about acquired causes, and 4 had information regarding both etiologies. Multiple genetic studies showed a strong association of As TAA with different genetic mutations. Contrary to commonly held beliefs, acquired causes, that is, dyslipidemia, diabetes, and atherosclerosis, were negatively associated with As TAA and positively associated with Des TAA. Hypertension was only associated with Des TAA and dissections (TAAD), not with As TAA. Multiple studies fulfilled the criteria of strength of association (n = 4), consistency (n = 9), specificity (n = 5), temporality (24), biological gradient (n = 3), plausibility (n = 38), biological coherence (n = 25), experiment (n = 4), and analogy (n = 6). Our literature review supports the hypothesis that As TAA is genetically mediated and Des TAA is predominantly an acquired pathology, and supports the argument for genetic testing in all cases of As TAA.