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Background Early reperfusion and first-pass effect are key procedural endpoints in large vessel occlusion stroke (LVOS) thrombectomy. Due to greater fibrin specificity, Tenecteplase may achieve higher early reperfusion rates compared to alteplase, yet impact of thrombolytic agents on first-pass effect remains unclear.Methods Consecutive anterior circulation LVOS patients receiving intravenous thrombolysis prior to endovascular treatment (EVT) at two U.S. stroke centers were reviewed. Early reperfusion was defined as eTICI ≥2b50 on initial angiography. First-pass effect was defined as eTICI 2c-3 after a single pass. Multivariable logistic regression identified predictors of early reperfusion and first-pass effect. Ordinal logistic regression assessed associations of thrombolytic agent, early reperfusion and first-pass effect with 90-day modified Rankin Scale (mRS) shift.Results Among 299 patients (Tenecteplase 201, alteplase 98), early reperfusion occurred in 60 (20.1%) and was more frequent with Tenecteplase compared to alteplase (24.4% vs 11.2%, aOR 2.54, 95% CI 1.19-5.42). Patients without early reperfusion were evaluated for first-pass effect. Of 239 patients, first-pass effect was less frequent with Tenecteplase compared to alteplase (30.3% vs 40.2%, aOR 0.50, 95% CI 0.27-0.91). Early reperfusion and first-pass effect each independently predicted better functional outcome, but functional outcomes were similar between Tenecteplase and alteplase overall.Conclusions We observed higher early reperfusion rates with Tenecteplase, but greater first-pass effect with alteplase, while functional outcomes were comparable. This suggests that higher early reperfusion rates with Tenecteplase may be offset by first-pass effect with alteplase, highlighting the importance of considering both reperfusion and procedural efficiency when comparing thrombolytic strategies.Disclosures K. Kline: None. T.M. Bielinski: None. G. Badger: None. V. Bohl: None. S. Hemmer: None. W. Stedman: None. O. Goren: None. J. Li: None. C. Schirmer: None. P. Hendrix: None.