Introduction: Tenecteplase (TNK) has been increasingly used in clinical practice for acute stroke thrombolysis. Comparisons with alteplase (ALT) for major adverse effects (AEs) in randomized trials have shown no differences between the thrombolytics. The relative rates of acute AEs of interest in real world clinical practice have not been fully investigated. Methods: We performed a retrospective comparison of acute AEs (see Table), including those not reliably reported in clinical trials, between the two drugs as used in real world clinical practice. Objective definitions of AEs were used for chart abstraction, to minimize user interpretation. For example, the criteria for hypotension included mean arterial pressure less than 65 mmHg sustained for at least 20 minute occurring within 6 hours of thrombolytic administration. Logistic regression analyses were performed adjusted for age, sex, NIHSS, thrombectomy, time from last known well to thrombolytic bolus, and pre-stroke history of antithrombotic medicines. Results: Sequential samples of 354 ALT and 472 TNK patients were analyzed. No differences in the adjusted logistic regression of acute AEs were seen between the two groups using a p<0.05 criterion (Table). Nominal trends for fewer hypotensive and symptomatic intracranial hemorrhage (sICH) events and more orolingual angioedema events for TNK were observed. Conclusion: In this retrospective quality improvement analysis, no significant differences in rates of acute AEs were observed between TNK-treated and ALT-treated patients. Larger samples may be needed to determine whether the nominal differences we observed in angioedema, hypotension, and sICH will prove to be significant.