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Background: The clinical significance of thrombophilic conditions in patients with acute ischemic stroke (AIS) remains incompletely understood.Methods: Among patients in the prospective Cornell AcutE Stroke Academic Registry (CAESAR), we included patients 18 to 65 years with AIS between 2011-2015 who had any hypercoagulability testing within 6 months of their index stroke. The exposure of interest was thrombophilia (see Table 1 for definitions). The primary outcome was moderate-to-severe stroke, defined as an NIH Stroke Scale (NIHSS) score >5. The secondary outcome was the inability to walk at the time of discharge. Data was imputed for missing outcome values. A doubly robust estimator and ordinal regression analyses were used to test the association between an underlying thrombophilic state and clinical outcomes.Results: Among 1,721 patients with AIS in the CAESAR registry, 196 patients (mean age 47 years; 51% female) met our eligibility criteria. Of these 196 patients, 47 (24%) were discovered to have a thrombophilic state. Excluding patients with missing outcomes, we found that 9 (22%; 95% confidence interval [CI], 15-29%) patients with thrombophilia had a moderate or severe stroke on admission, as compared to 35 (32%; 95% CI, 25-40%) patients without thrombophilia (p=0.22). At the time of hospital discharge, 8 (17%; 95% CI, 12-23%) patients with thrombophilia were unable to walk, as compared to 31 (21%; 95% CI, 15-27%) patients without thrombophilia (p=0.49). After imputing data on missing outcomes and adjusting for demographics and vascular risk factors, an underlying thrombophilic state was not associated with moderate-to-severe stroke on admission (odds ratio [OR], 0.8; 95% CI, 0.3-2.2) or poor ambulatory status at discharge (OR, 1.7; 95% CI, 0.7-4.1).Conclusions: In a single-center study of young adults with AIS, we found no association between an underlying thrombophilic state and stroke severity or ambulatory status at discharge.