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Introduction: IV alteplase (tPA) decreases long-term disability from acute ischemic stroke (AIS). Many patients do not receive tPA due to mild stroke symptoms (NIHSS < 5), even when they meet criteria for treatment, perhaps due to concern that risk of treatment in these populations outweighs benefit. This study compares outcomes for acute ischemic stroke (AIS) patients with mild symptoms who received tPA versus those who did not.Methods: Data obtained from a multi-hospital system’s Get With The Guidelines registry included AIS patients with admission NIHSS of less than five who were discharged between January 2014 and December 2016 and presented within 4.5 hours of onset of stroke symptoms. Patients were excluded if they had an in-hospital stroke or were not treated due to a reason other than mild stroke symptoms. Outcomes included discharge modified Rankin Scores (mRS) categorized as no-to-mild disability (mRS≤2) vs moderate disability to death (mRS≥3), hospital length of stay (LOS) and discharge disposition. Generalized linear and Cox proportional hazard models were used to compare outcomes adjusting for admission NIHSS, age, mode of arrival, gender, and last known well to arrival time.Results: A total of 854 patients met inclusion criteria with 53.5% (n=457) treated with tPA and 46.5% (n=397) excluded from treatment for mild stroke only. Median age was 68 (interquartile range = 57 to 77) years and 47% were female. Patients who were excluded from treatment for mild stroke were 2.33 times more likely to have discharge mRS≥3 than patients with mild symptoms treated with tPA (p=0.014). There were no statistically significant differences in likelihood of discharge to home or length of stay.Conclusion: Patients with mild strokes excluded from tPA treatment for mild symptoms were more likely to be disabled based on discharge mRS than those treated with tPA. Physicians should consider treating patients with mild symptoms with tPA to improve patient outcomes.