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Introduction Hemorrhagic transformation (HT) complicates intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). Because antiplatelets are widely prescribed for secondary prevention, their effect on post-IVT bleeding warrants clarification. Prior studies disagree, and pooled analyses show only modest excess risk. We tested whether baseline antiplatelet therapy independently predicts HT after IVT.Methodology We retrospectively reviewed 317 consecutive AIS patients treated at a comprehensive stroke center from December 2019 to January 2022. Pre-hospital antiplatelet exposure was recorded, and HT was defined by ECASS III. Demographic, clinical, laboratory, and imaging data were extracted. Subgroup analysis included only patients who received IVT. Fisher exact test with odds ratios (OR) assessed the association between antiplatelet use and HT, with p < 0.05 considered significant.Results The cohort was 55.8 percent male, median age 68 years (27 to 99), mean body-mass index 27.9 kg m−2. Hypertension, hyperlipidemia, diabetes, coronary disease or myocardial infarction, prior stroke or transient ischemic attack, and atrial fibrillation were present in 76.6, 68.5, 38.2, 26.5, 25.2, and 18 percent respectively. At admission 24.3 percent used antiplatelets only, 11.3 anticoagulants only, 12.3 both, and 52.1 neither. Mean values were NIHSS 8, ASPECTS 9, systolic pressure 154 mmHg, glucose 152 mg dL−1, platelet count 251 × 10(9) L−1. Occlusions most often involved M1 (16.7 percent) and internal carotid (12). Endovascular therapy was undertaken in 110 patients (34.7) and IVT in 128 (40.4). Adverse events comprised intracranial hemorrhage 24, gastrointestinal bleeding 6, hospice transition 1, in-hospital death 13. Among 77 patients on antiplatelets only, 47 received IVT and 3 developed HT (OR 0.68, p = 0.76). Among 201 without antiplatelets, 99 received IVT and 10 developed HT (OR 1.47, p = 0.76). HT risk did not differ significantly.Conclusion Baseline antiplatelet therapy was not linked to increased hemorrhagic transformation after intravenous thrombolysis for acute ischemic stroke in this single-center retrospective study. These findings support the safety of IVT in patients taking antiplatelets. Limitations include retrospective design, single site, and moderate sample size; larger prospective multicenter studies with standardized imaging criteria are warranted.Disclosures S. Vyas: None. S. Nageeb: None. J. Haimi: None. S. Bozkurt: None. I. Abualnadi: None. Z. Singh: None. U. Panchal: None. N. Gadallah: None. P. Sharma: None. H. Zacharatos: None. B. Jankowitz: None.