Introduction: The American Stroke Association Guidelines on acute ischemic stroke (AIS) thrombolytic treatment endorse the use of tenecteplase (TNK) weakly (IIb) based on moderate quality (B-R) evidence. The use of alteplase for AIS is strongly recommended (I) with high quality (A) of evidence. Despite this, many healthcare systems have transitioned to the use of TNK based on limited clinical trial data. Our study presents real world outcome data comparing AIS patients treated with TNK vs alteplase. Methods: Data were retrospectively abstracted from AIS patients treated with IV thrombolytic (IVT) or IVT and endovascular therapy (EVT) discharged between 1/1/2019-6/30/2022 . Patients were grouped into alteplase w/wo thrombectomy and TNK w/wo thrombectomy. Primary outcomes were discharge disposition, complications (sICH, serious systemic hemorrhage), door to needle and door to device times, treatment complications and post-EVT TICI score. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) are reported for likelihood to receive IVT within 45 minutes and 30 minutes of arrival for the IVT group, adjusting for sex, race, admit NIHSS, and previous stroke. Results: 3733 patients were included in the IVT group: 90.7% received alteplase, 9.3% received TNK. 814 patients received IVT and EVT: 90% received alteplase and 10% received TNK. In the IVT group, the median [Q1, Q3] DTN for alteplase was 48 [35, 66] minutes TNK was 45.5 [34.75, 63.25] (p=0.067). There was no significant difference in the likelihood of receiving IVT within 45 minutes and 30 minutes between the two drugs. Patients with higher admit NIHSS were more likely to receive IVT within 45 minutes (AOR 1.031 95% 1.021, 1.041 p Conclusion: In our study there were no differences in benefit, risk, or treatment logistics between alteplase and tenecteplase when used in treating acute ischemic stroke. Recanalization of large vessel occlusion prior to endovascular thrombectomy was not analyzed but will be the subject of study in this cohort.