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Introduction: IV alteplase (tPA) is recommended but not FDA approved in the US in the 3-4.5 hour time window. Current guidelines recommend treatment for those under age 80 with no preceding history of stroke and diabetes. This study analyzes treatment rates and reasons for exclusion from a large multistate stroke registry.Methods: Data obtained from a multi-hospital system’s GWTG Registry included acute ischemic stroke (AIS) patients discharged January 2012-May 2017 who arrived within 4.5 hours of last-known-well. Exploratory analyses reviewed tPA treatment rates and exclusion practice patterns for all AIS patients who arrived in the 0-3 and 3-4.5 hour windows and AIS patients over the age of 80 or with a history of diabetes and previous stroke who arrived in the 3-4.5 hour window.Results: A total of 6,392 patients met inclusion criteria with 83.5% (n=5,337) arriving in the 0-3 hour window and 16.5% (n=1,055) in 3-4.5 hours. Treatment rates in the 0-3 hour and 3-4.5 hour windows were 41.1% and 9.8%, respectively. Of patients arriving in the 0-3 hour window, 55.5% had a documented exclusion compared to 57.4% in the 3-4.5 hour window. In the 0-3 hour window, the top exclusions were rapid improvement (42.5%), mild stroke (37.1%) and bleeding risk (9.1%). In the 3-4.5 hour window, top exclusions were rapid improvement (28.0%) and mild stroke (27.0%). Among patients over 80 arriving in the 3-4.5 hour window (n=429), the tPA treatment rate was 3.3% and 62.9% had a documented reason for exclusion. The top reasons for exclusion were age over 80 years (25.6%) and rapid improvement (19.6%). Among patients with a history of both previous stroke and diabetes arriving in the 3-4.5 hour window (n=643), the tPA treatment rate was 8.7% and 61.4% had a documented exclusion. The top reasons for exclusion were rapid improvement (23.5%) and stroke too mild (23.5%). Only 6.8% were excluded based on a preceding history of diabetes and stroke.Conclusions: Treatment rates were dramatically lower in the 3-4.5 hour time window. The majority of patients over 80 presenting in the 3-4.5 hour time window were excluded from treatment based on age. Contrary to professional guideline recommendations, a preceding history of stroke and diabetes is rarely documented as the cause for not treatment.