Background and Objectives Intravenous thrombolysis (IVT) followed by endovascular thrombectomy (EVT) improves functional outcomes in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). There are limited data on the effect of thrombolysis-to-puncture time (TTP) on outcomes in patients with AIS undergoing IVT plus EVT. Methods We selected 1,104 patients receiving IVT + EVT for anterior circulation LVO stroke from 2 prospective nationwide registries (259 cases from ANGEL-ACT in China: November 2017 to March 2019, 845 cases from German Stroke Registry-Endovascular Treatment in Germany: June 2015 to December 2019). Based on the TTP, eligible patients were divided into 4 groups (<= 30 min, 31-50 min, 51-70 min, and >70 min). The radiologic and clinical outcomes (e.g., successful recanalization [modified Thrombolysis in Cerebral Infarction score of 2b-3] at final angiogram, modified Rankin Scale [mRS] score of 0-2 at 90 days, any intracranial hemorrhage [ICH], and symptomatic ICH within 24 hours) among the 4 groups were compared by chi(2) tests for trend and using multivariable logistic regression models. Results In the 4 groups from <= 30 min to >70 min, 226, 282, 230, and 366 patients were included, respectively. An increased TTP was associated with a lower chance of successful recanalization (p = 0.016) and mRS score 0-2 (p = 0.002). Compared with the group of <= 30 min, the group of >70 min was less likely to achieve successful recanalization (adjusted odds ratio [OR] = 0.47, 95% CI 0.25-0.89) and the groups of 50-70 min and >70 min had a reduced probability of mRS score 0-2 (adjusted OR = 0.50, 95% CI 0.33-0.78; adjusted OR = 0.56, 95% CI 0.37-0.85). No significant differences were found for any ICH or symptomatic ICH among the 4 groups after adjustment with potential confounders. Discussion Delay from thrombolysis to puncture should be minimized when considering bridging IVT before EVT for patients with AIS due to anterior circulation LVO. Further studies are warranted to verify and expand on these findings.