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Background: It is uncertain whether history of prior ischemic stroke is associated with an increased risk of adverse outcomes in diabetic patients treated with intravenous tissue plasminogen activator (IV-tPA) for acute ischemic stroke.Methods: Using administrative claims data, we identified all diabetic adults with acute ischemic stroke who received IV-tPA at California, New York, or Florida hospitals between 2005-2013. Our exposure of interest was prior ischemic stroke. Our primary outcome was intracerebral hemorrhage (ICH) and our secondary outcomes were inpatient mortality and unfavorable discharge disposition (skilled nursing facility, subacute care center, chronic rehabilitation center, hospice, or death). We used multivariable logistic regression to compare the rate of outcomes in diabetic patients with and without a history of prior ischemic stroke.Results: We identified 12,786 diabetic patients (mean age 70.7 [±13.1] years) who received IV-tPA for AIS, of whom 1,112 (8.6%) had a history of prior ischemic stroke. Among all patients, 699 (5.5%; 95% confidence interval [CI] 5.1-5.9%) developed ICH and in-hospital death occurred in 11.9% (95% CI, 11.3-12.5%). After adjusting for demographics, stroke risk factors, and the Elixhauser comorbidity index, history of prior ischemic stroke was not associated with an increased risk of ICH (OR, 0.8; 95% CI, 0.6-1.1, P = 0.26), inpatient mortality (OR, 0.9; 95% CI, 0.7-1.1, P=0.22), or unfavorable discharge disposition (OR, 1.1; 95% CI, 0.9-1.2, P=0.57).Conclusion: Among diabetic patients who received IV-tPA for acute ischemic stroke at three large states in the U.S., history of prior ischemic stroke was not associated with an increased risk of ICH, inpatient death, or unfavorable discharge disposition. Further evaluation is necessary to assess whether administration of IV-tPA within the extended 3-4.5 hour window for acute ischemic stroke is safe for diabetic patients with prior stroke.