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Introduction: Blood pressure (BP) control prior to and after administration of either tenecteplase or alteplase (TNK/tPA) for acute ischemic stroke (AIS) is essential to ensure timely administration of therapy and minimize adverse events. Labetalol and nicardipine are recommended options to treat hypertension for patients eligible to receive emergency reperfusion therapy. Limited data exists comparing the hemodynamic effects and safety of these agents in AIS. This study evaluated the impact of intravenous labetalol (LAB) versus labetalol plus nicardipine (LAB-NIC) on target BP in AIS patients receiving TNK/tPA. Methods: This single-center, retrospective cohort study included adult patients between 4/1/2016-3/31/2025, who received thrombolytic therapy for AIS and required antihypertensives with either LAB or LAB-NIC in the emergency department. Patients were excluded if they were pregnant, transferred from an outside hospital, missing pre-TNK/tPA vitals, or received non-study antihypertensives before TNK/tPA. The primary outcome was time to BP < 185/110 mmHg before TNK/tPA. Secondary outcomes included absolute changes in systolic blood pressure (SBP), door to needle time, and SBP < 90 mmHg. Data were analyzed using SPSS. Results: Of the 575 patients screened, 87 were evaluated (68 LAB, 19 LAB-NIC). Baseline characteristics including NIHSS were similar between groups. Time to BP < 185/110 mmHg before TNK/tPA was not different between groups, 44 (21,60) LAB vs 39 (27,62) LAB-NIC, min, p=0.98. However, patients who received multiple doses of labetalol vs those who received one dose of labetalol plus nicardipine, the time to BP < 185/110 mmHg before TNK/tPA was faster with LAB-NIC, 55 (33,94) LAB v 27 (20,46) LAB-NIC, min, p=0.02). Door-to-needle time was similar, 61.5 (45.2,84.2) LAB vs 68.0 (55.0,106.0) LAB-NIC, min, p=0.92. SBP < 90 mmHg up to 24 hours after TNK/tPA was similar, 12% LAB vs 10% LAB-NIC, p=0.99. Conclusions: Effective BP control is important in AIS to reduce the time to TNK/tPA administration and adverse events. Overall, time to BP < 185/110 mmHg was not different between groups. However, when more than one dose of labetalol is needed to achieve eligibility for thrombolytic therapy, early initiation of nicardipine may reduce the time to goal blood pressure.