Background: Hemorrhagic conversion (HC) is one of the most feared complication of tissue plasminogen activator (tPA) use for acute ischemic stroke (AIS). Prior studies have shown very high mortality rates for HC, but are limited due to sampling. We aimed to assess predictors of HC after IV tPA in AIS using a large and representative national patient registry. Method: The Nationwide Inpatient Sample (NIS) were analyzed for the years 2002-2014. AIS were identified using the ICD-9-CM 433.xx-436 as a primary diagnosis. tPA utilization was identified with procedure code 99.10, HC with ICD-9 431 as secondary diagnosis. Patient demographics as well as common medical comorbidities were applied to model. Cochran Armitage trend test and survey logistic regression procedure to analyze trends and predictors. Results: Of 264,643 AIS who received tPA, 21,418 (8.09%) developed HC. In multivariable regression analysis, increasing age, atrial fibrillation, septicemia, mechanical thrombectomy, alcoholism, epilepsy, malignancy and diabetes were associated with higher odds of HC (Table). Women and admissions in west region were associated with lower odds of HC. Race, type of hospital, and prior stroke were not associated with increased or decreased odds of HC. Conclusion: In this nationally representative study, we observed several factors significantly associated with hemorrhagic conversion, some of which may be potentially modifiable to reduce the odds of this worrisome outcome. Future studies should consider factoring some of these variables into prognostic scores or testing interventions to ameliorate them.