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Introduction: Even though tissue plasminogen activator (tPA) has unequivocally shown to improve outcomes in Acute Ischemic stroke (AIS), its utilization remains low due to various concerns/contraindications. Many clinicians are concerned about the risk of hemorrhage after tPA in patients on anti-coagulation (AC). With the rise of AC use, we aimed to explored the relationship between anticoagulation use and hemorrhagic conversions (HC) in patients treated with IV tPA in a large and representative national patient registry.Method: We analyzed Nationwide Inpatient Sample (NIS) and Healthcare Cost and Utilization Project (HCUP) data for years 2002-2014. We identified AIS with ICD-9-CM codes 433.xx-436, IV tPA with procedure code 99.10, and HC with ICD-9 431. Anticoagulation use was identified by previously validated ICD-9-CM codes. Parametric tests and survey logistic procedure were used to analyze group comparison and multivariate regression.Results: A total of 264,643 patients with AIS received IV tPA, of which 12,690 (4.8%) were on AC prior to admission. Unadjusted, the frequency of HC was higher among AC group (9.1% v 8.0%; p<0.001). However, after adjusting for confounders with multivariate analysis, there was no difference in HC between AC and ‘not on AC’ group [OR 0.87; 95% Confidence Interval(CI) 0.75-1.01; p=0.071]. Additionally, there was no difference in in-hospital mortality [OR 0.91; 95% CI 0.79-1.05; p=0.178] and discharge to home [OR 1.1; 95% CI 0.99-1.2; p=0.05] among AC and ‘not on AC’ group.Conclusion: Our study shows, AC use prior to AIS onset is not associated with higher HC with tPA use. Moreover, no significant differences in outcomes were observed in AC and ‘not on AC’ group. Being on AC should not be a prohibitive factor for tPA utilization in AIS patients. Further prospective studies, that includes precise anticoagulant measurements, are required to better understand the relationship between AC use and HC.