Introduction: There are no data to support the hypothesis of an increased risk of symptomatic ICH (sICH) with the later 3-4.5h IV-tPA treatment window, compared to the <3h window. Hypothesis: There is a significant difference in the odds of suffering a sICH if treated with IV-tPA <3h, compared to 3-4.5h. Methods: This was a 6-year retrospective observational cohort study. All adult (≥18 yrs) patients admitted with an ischemic stroke between 1/2010-6/2015 and treated with IV-tPA were included in the study. Patients receiving IA treatment were excluded (n=244). Outcomes for this study were sICH (4-point increase in NIHSS within 36h with new ICH seen on CT), in-hospital mortality and favorable discharge mRS (≤2). Chi-squared, Fisher’s exact and Wilcoxon rank-sum tests were used to compare proportions and medians between groups. Multivariate, stepwise logistic regression was used to assess differences in the odds of outcomes; entry and exit criteria for covariates were p=0.20 and p=0.10. Results: 561 (90%) were treated <3h, 64 (10%) were treated 3-4.5h. A significantly larger proportion of patients in the IV-tPA ≤3h group, compared to the IV-tPA 3-4.5h group were aged ≥80 years and white (both p<0.01). 13 (2%) patients suffered a sICH. There were no significant demographic or clinical differences between patients suffering a sICH and those who did not. Patients treated with IV-tPA <3h had a significant 76% decreased odds of suffering a sICH (Table 1); no covariates found. 70 (11%) of patients died. After adjustment, patients treated <3h had a significant 59% reduction in the odds of dying (Table 1). 251 (42%) were discharged with a favorable discharge mRS. After adjustment, patients treated <3h had a 71% increase in the odds of a favorable outcome, trending toward significance (Table 1). Conclusions: tPA treatment windows impact sICH, mortality and favorable mRS rates. Ensuring thrombolytic therapy is received <3h from symptoms is vital for decreasing the risk of suffering an sICH.