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. Results146 patients received tenecteplase and 307 received alteplase. Tenecteplase shortened door-to-IVT time (33 vs. 39 min, P < 0.001) 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 (Pinteraction = 0.034): tenecteplase achieved higher ER rates when IVT-to-puncture time was < 60 min (17.2% vs. 5.0%, aOR, 4.13 [95% CI 1.24-13.74]). With IVT-to-puncture time >= 60 min, ER rates were similar (17.2% vs. 16.8%, aOR 0.91 [95% CI 0.43-1.91]). No ER differences were noted across occlusion sites, clot burden, NIHSS, sex, and age. At 3 months, tenecteplase reduced disability rates (mRS 0-3: 73.5% vs. 65.7%, P = 0.041). Functional independence (mRS 0-2) was 57.4% with tenecteplase and 53.1% with alteplase (P = 0.301). 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.