Abstract Body: Aneurysms originating in the ascending aorta are associated with increased risk of aortic dissection. A large proportion of patients with ascending thoracic aortic aneurysms (ATAA) have bicuspid aortic valve (BAV), a congenital malformation of the aortic valve. ATAA in patients with BAV share smooth muscle cell (SMC) dysfunction and extracellular matrix (ECM) degradation with ATAA arising in individuals with morphologically normal trileaflet aortic valves (TAV), but underlying pathways differ. Building on our prior work indicating higher oxidative stress in BAV-ATAA, we hypothesize this relates to SMC mitochondrial dysfunction causing metabolic reprogramming in BAV-ATAA. In primary SMCs from BAV-ATAA, TAV-ATAA, and non-aneurysmal TAV (TAV-NA) aortas, Seahorse profiling showed that basal and ATP-linked oxygen consumption rates (OCR) were similar across groups, while maximal respiration and spare capacity were increased in both aneurysm cohorts, indicating greater ability to meet metabolic demand. BAV-ATAA SMCs exhibited elevated proton leak and higher non-mitochondrial respiration, consistent with mitochondrial inefficiency and inflammatory/oxidase activity. Total cellular ATP content was higher in both aneurysm groups, implicating non-mitochondrial ATP sources and altered energy handling. Extracellular acidification rate (ECAR) was selectively increased in BAV-ATAA and total ATP production rate rose only in BAV-ATAA despite unchanged ATP-linked OCR aligning with a glycolytic shift. Markers of mitochondrial biogenesis were heightened in BAV-ATAA: mitochondrial transcription factor A (Mt-TFA) expression and mitochondrial DNA (mtDNA) content increased versus TAV-NA and TAV-ATAA. Bulk RNA-seq and proteomics with gene set enrichment analysis (GSEA) revealed coordinated upregulation of reactive oxygen species (ROS), glycolysis, oxidative phosphorylation pathways, and superoxide metabolic processes gene sets in BAV-ATAA relative to TAV-ATAA. Together, these findings delineate a BAV-specific bioenergetic phenotype characterized by preserved baseline respiration, enhanced metabolic flexibility but reduced efficiency under stress, and preferential engagement of glycolysis. Metabolic markers and targeted modulation of proton leak, ROS and glycolytic flux may enable BAV-specific risk stratification and therapy.