Objective: To determine the outcomes related to thrombolytic treatment of an acute ischemic stroke secondary to an arterial dissection in a large national cohort. Design: Retrospective database study. Setting: Nationwide Inpatient Sample data files from 2005 to 2008. Patients: We determined the frequency of underlying arterial dissection among patients with acute ischemic stroke treated with thrombolytic treatment and associated in-hospital outcomes. Main Outcome Measures: All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. Results: Of the 47 899 patients with ischemic stroke who received thrombolytic treatment, 488 (1%) had an underlying dissection. The intracranial hemorrhage rates did not differ between patients with ischemic stroke with orwithout underlying dissection who received thrombolytic treatment (6.9% vs 6.4%). After adjusting for age, sex, hypertension, diabetes mellitus, renal failure, congestive heart failure, and hospital teaching status, presence of dissection was associated with higher rates of moderate disability (odds ratio, 2.8; 95% confidence interval, 1.7-4.6; P<.001) at discharge. The interaction terms between dissection and thrombolytic treatment among all patients with ischemic stroke for predicting in-hospital mortality (P=.84) and minimal disability (P=.13) were not statistically significant. Conclusions: The adjusted rate of favorable outcomes is lower among patients with ischemic stroke with underlying arterial dissection following thrombolytic treatment compared with those without underlying dissections. However, the observed lower rates are not influenced by thrombolytic treatment.