BACKGROUND AND OBJECTIVE: Aortic aneurysms, including abdominal (AAA) and thoracic (TAA), pose significant challenges due to their rupture risk and complex pathophysiology. While aspirin has been proposed to manage aneurysm progression, evidence remains limited. This retrospective, single-center study used AI-driven methods to examine the association between aspirin therapy and aneurysm growth. METHODS: The study, at the University of Kentucky Healthcare, utilized de-identified electronic health record data from 2010 to 2023. To evaluate platelet counts changes, Cohort 1 included patients with AAA or TAA and matched healthy controls. Cohort 2 included AAA or TAA patients who had at least two imaging studies. Extraction of aortic diameters utilized an advanced AI-based natural language processing (NLP) algorithm to identify and extract relevant text strings related to aortic dimensions. Multivariable-adjusted linear regression analyses assessed the impact of aspirin on aneurysm progression. RESULTS: Cohort 1 included 11,538 participants: 5,774 controls, 3,439 with AAA, and 2,325 with TAA. Platelet counts were significantly lower in patients with aortic aneurysms compared to controls, though they were not considered thrombocytopenic. Cohort 2 included 302 AAA and 141 TAA patients. Subgroup analysis revealed that aspirin use was associated with increased AAA progression in females with small aneurysms (<
50 mm). Further, aspirin therapy showed no significant impact on the annualized change in aneurysm diameter for TAA or for males with AAA. CONCLUSION: Our findings suggest aspirin's effectiveness varies by sex and potentially aneurysm size, underscoring the need for further research to refine antiplatelet therapy guidelines for aortic aneurysms.