Background: The safety of thrombolysis for acute stroke in patients with cancer is not well established. Our aim is to study the outcomes following thrombolysis in stroke patients with cancer. Methods: Acute ischemic stroke (AIS) patients who received thrombolysis were identified from the 2009 and 2010 Nationwide Inpatient Sample using ICD-9 codes. Patients with cancer associated strokes (CS) and non-cancer strokes (NCS) were compared based on demographics, comorbidities, and outcomes. Results: There were 1,135,574 AIS in 2009-2010. Thrombolysis was administered to 807 patients out of 50,437 CS (1.6%), and 31,769 patients out of 1,085,137 non-cancer strokes (2.9%). The prevalence of stroke risk factors such as hypertension (p<0.001) and hyperlipidemia (<0.001) were significantly higher in non-cancer strokes (NCS). CS had a significantly higher percentage of patients in the third and fourth Elixhauser quartiles (p<0.001). Hospitals with > 450 beds were more likely to treat cancer patients with thrombolysis for acute stroke (p=0.011), while the hospital teaching status did not play a significant role. In the univariate analysis, CS was associated with a lower proportion of home discharge in the overall thrombolytic treatment group (OR: 0.57, CI: 0.48-0.68, p<0.001) but mortality was not significant. ICH rates were also comparable in the two groups (6.3% vs 6.4%, p= 0.927). In the regression model, there was no difference in mortality or ICH rates between CS and NCS following thrombolysis. Subgroup analysis of IV thrombolysis only and endovascular treatment also showed no difference in outcomes. Another subgroup analysis showed that compared to liquid cancers, patients with solid had worse home discharge (OR: 0.178, CI: 0.109-0.290, p<0.001), and higher in-hospital mortality (OR: 3.018, CI: 1.37-6.646, p=0.006) following thrombolysis. Metastatic cancers had poorest outcomes. Conclusions: Thrombolytic therapy for acute stroke in patients with cancer is not associated with increased risk of ICH or in-hospital mortality. However, careful consideration of the cancer subtype may help delineate the subset of patients with poor response to thrombolytic therapy. Prospective confirmation and attention to long-term outcomes is warranted.