BACKGROUND: The comparative efficacy of tenecteplase versus alteplase in achieving early recanalization (ER) before mechanical thrombectomy (MT) for large-vessel occlusion (LVO) remains uncertain. METHODS: This study was a retrospective analysis of prospectively collected data of consecutive patients with LVO underwent intravenous thrombolysis (IVT) and brain angiography between January 2022 and December 2023. ER was defined as ≥ 50% reperfusion or absence of retrievable thrombus on initial angiography. RESULTS: 146 patients received tenecteplase and 307 received alteplase. Tenecteplase shortened door-to-IVT time (33 vs. 39 min, P <
0.002) and door-to-puncture time (97 vs. 109 min, P = 0.039) compared to alteplase. Overall ER rates did not differ significantly (17.1% vs. 12.1%, P = 0.223). However, a significant interaction was observed between thrombolytic agent and IVT-to-puncture time (P CONCLUSIONS: Real-world observations reveal tenecteplase has increased ER rates compared to alteplase within 1 h of IVT and reduced disability in LVO patients. Further randomized trials are warranted to evaluate the effect of tenecteplase rapid bridging mechanical thrombectomy.