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Background and Purpose: The ASA/AHA guidelines recommend a fixed dose of 90 mg of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) for acute stroke patients weighing more than 100 kg. We aimed to determine if body weight >100 kg (and receiving <0.9 mg/kg dose) independently influence patient clinical outcomes following IV rt-PA treatment., Methods: We pooled data from IV rt-PA treatment arms from 3 randomized controlled clinical trials; NINDS IV rt-PA study, Interventional Management of Stroke 3 and ALIAS (part 1 and 2). Baseline characteristic, hospital course and 90-day mRS were compared between patients >100 kg and those ≤100 kg body weight. Multivariate logistic regression model was used to identify the independent effect of >100 kg body weight on favorable 90-day outcome (defined as mRS 0-2), the rate of symptomatic intracranial hemorrhage, and poor 90-day outcome (mRS 4-6)., Results: Among 873 patients treated with IV rt-PA, a total of 105 (12%) subjects had body weight >100 kg. Compared with patients having ≤100 kg body weight, the rate of favorable outcome at 90 days was not significantly different among patients with >100 kg body weight (OR: 0.99; 95% CI: 0.91-1.01; p=0.91) , after adjusting for potential confounders. The ordinal analysis did not show any significant shift in the distribution of 90-day mRS score in patients with >100 kg body weight (OR, 0.93; 95% CI, 0.64-1.37; P = 0.74) CONCLUSIONS: There was no reduction in the rate of favorable outcome in patients with acute ischemic stroke with body weight >100 kg who received <0.9 mg/kg dose of IV rt-PA. Our results support the current recommendations in the ASA/AHA guidelines., (Copyright © 2018. Published by Elsevier Inc.)