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Background: The ASA/AHA guidelines recommend a fixed dose of 90 mg of intravenous recombinant tissue plasminogen activator(rt-PA) for acute stroke patients weighing more than 100 kilograms(kg). Previous analyses in small studies have suggested that the magnitude of benefit with IV rt-PA is lower in patients with body weight >100 kg. We determined 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 trials; NINDS IV rt-PA study, IMS-III and Albumin Treatment of Acute Ischemic Stroke(ALIAS part 1 and 2). Patients demographic, stroke severity, comorbidities, hospital outcome and 90-day modified Rankin Scale(mRS) were compared between patients >100 kg and those ≤100 kg body weight(defined by estimated weight). Multivariate logistic regression model was used to identify independent effect of >100 kg body weight on 90-day favorable outcome(defined as mRS 0-2). An ordinal analysis of the mRS was also performed.Results: Among 977 patients treated with IV rt-PA, total of 111 subjects had body weight >100 kg(11% of all patients). The mean age(±SD) for the patients with weight >100 Kg was significantly lower(60±11 versus 68±13, p<0.0001). The median admission NIHSS score was not different between the two groups(12 versus 13, p=0.08). Patients with weight >100 kg had higher rates of history of hypertension, diabetes mellitus, and hyperlipidemia. Patients with body weight >100 kg had longer period(days±SD) of hospitalization(11±14 versus 8±7, p=0.04). Compared with patients with ≤100 kg body weight, the rate of favorable outcome at 90 days was not significantly different among patients with >100 kg body weight[OR; (95% CI): 0.99 (0.91-1.04)p=0.91], after adjusting for potential confounders. The ordinal analysis did not showed any significant shift in the distribution of scores on the mRS in patients with >100 kg body weight(OR, 0.93; 95% CI, 0.64 to 1.37; P = 0.74).Conclusion: Body weight >100 kg(and receiving <0.9 mg/kg dose) did not reduce the benefit of IV rt-PA treatment in acute ischemic stroke patients. Our results support the current recommendations in the ASA/AHA guidelines.