IntroductionWomen are at higher risk of stroke mimics; however, the underlying reasons are unclear. MethodsIn this retrospective cohort study of the 2016–2020 National Inpatient Sample database, we identified patients treated with intravenous thrombolysis (IVT). Demographic information, vascular risk factors, comorbidities, and presence of known risk factors for stroke mimics (seizures, migraines, demyelinating diseases, psychiatric illnesses, and functional neurological disorders [FND]) were identified using ICD-10 codes. Rates of no cerebral infarction (NCI) were compared between men and women. Mediation analyses were conducted to identify significant drivers of sex-specific differences in the rate of NCI. Results174,995 IVT-treated patients were identified; 41,605 (23.8 %) had NCI. Female patients had significantly higher rates of NCI compared to men (26.2 % vs. 20.9 %, p < 0.001). Women had significantly higher rates of stroke mimic risk factors (seizures, migraines, demyelinating disease, anxiety, depression, FND, and electrolyte derangements; all p < 0.001). Mediation analyses revealed that 39.8 %, 19.1 % of female sex's association with higher rates of NCI were mediated by higher rates of migraines and FND among women, respectively (both p < 0.001). ConclusionsIVT-treated women were more likely to have NCI than men. This relationship was largely mediated by higher rates of migraine and FND among women.