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Introduction: There are preliminary data indicating that pretreatment with dual antiplatelet therapy (DAPT) may increase the risk of symptomatic intracranial hemorrhage (sICH) following intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). We sought to identify the safety and efficacy of pretreatment with DAPT in IVT for AIS in a prospective, multi-center study.Methods: AIS patients treated with IVT during a five-year period in two tertiary care stroke centers were evaluated. Baseline stroke severity and early hypodensity on baseline CT were assessed by NIHSS-score and ASPECTS by certified physicians. Three-month functional status was assessed using modified Rankin Scale (mRS). We compared the following outcomes between DAPT (+) and DAPT (-) patients before and after propensity score matching (PSM): 1.sICH, 2. asymptomatic intracranial hemorrhage (aICH) 3. favourable functional outcome (FFO; mRS scores of 0-1), 4. 3-month mortality.Results: Out of total 790 IVT-treated AIS patients, we identified 58 (7%) pretreated with DAPT (mean age 68±13 years; 57% men; median NIHSS-score 8, IQR: 4-14). The two groups did not differ (p>0.05) in terms of sICH [DAPT(+): 3% vs. DAPT(-): 3%], FFO (64% vs. 50%) and 3-month mortality (9% vs. 9%) in unmatched analyses. DAPT pretreatment was associated with higher odds of aICH before (17% vs. 6%) and after adjustment (OR: 2.4; 95%CI: 1.1-5.5) for potential confounders. After PSM, patients with (n=41) and without (n=82) DAPT pretreatment did not differ in any of the baseline characteristics. The differences in rates of all outcome events were non-significant in the two groups including sICH (2% vs. 1%, p=0.63), aICH (17% vs. 7%, p=0.06) and 3-month mRS (p=0.60; Figure).Conclusions: Pretreatment with DAPT is not associated with higher rates of sICH or three-month mortality and does not reduce the odds of FFO following IVT for AIS. IVT should not be withheld in otherwise eligible candidates due to pretreatment with DAPT.