Background and Purpose - We report the relation of onset-to-treatment time and door-to-needle time with functional outcomes and mortality among patients with ischemic stroke with imaging-proven large vessel occlusion treated with intravenous alteplase. Methods - Individual patient-level data from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration were pooled from 7 trials that randomized patients to mechanical thrombectomy added to best medical therapy versus best medical therapy alone. Analysis was restricted to patients who received alteplase directly at the endovascular hospital. The primary outcome was disability defined on the modified Rankin Scale at 3 months. Results - Among 601 patients, mean age was 66.0 years (SD, 13.9), 50% were women, and median National Institutes of Health Stroke Scale score was 17. Onset-to-treatment time was median 125 minutes (interquartile range, 90-170). Door-to-treatment time was median 38 minutes (interquartile range, 26-55). Each 60-minute onset-to-treatment time delay was associated with greater disability at 90 days; the odds of functional independence (modified Rankin Scale, 0-2) at 90 days was 0.82 (95% CI, 0.66-1.03). With each 60-minute delay in door-to-needle time; the odds of functional independence was 0.55 (95% CI, 0.37-0.81) at 90 days. The absolute decline in the rate of excellent outcome (modified Rankin Scale, 0-1 at 90 days) was 20.3 per 1000 patients treated per 15-minute delay in door-to-needle time. The adjusted absolute risk difference for a door-to-needle time <30 minutes versus 30 to 60 minutes was 19.3% for independent outcome (number-needed-to-treat ≈5 to gain 1 additional good outcome). Symptomatic intracranial hemorrhage occurred in 3.4% of patients, without a significant time dependency: Odds ratio, 0.74 (95% CI, 0.43-1.28). Conclusions - Faster intravenous thrombolysis delivery is associated with less disability at 3 months among patients with large vessel occlusion.