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Introduction: Although alterations in fibrinogen and fibrinogen degradation products are well-established after intravenous tissue plasminogen activator (IVtPA) in acute stroke, IVtPA is not recognized to cause markedly abnormal international normalized ratio (INR).Methods: With IRB approval, we prospectively screened 99 consecutive acute stroke patients who received IVtPA admitted from November 1, 2015 to July 1, 2016. Laboratory tests including INR, activated partial thromboplastin time (aPTT), fibrinogen, and d-Dimer were drawn at intervals of 6, 12, 24, and 48 hours. Data was collected on patient demographics, last known normal (LKN), IVtpA dose and timing, and National Institutes of Health Stroke Scale (NIHSS). Post-IVtPA coagulopathy was defined as INR ≥ 1.5. Reference range for fibrinogen was 190 - 395 mg/dL.Results: Among 44 patients prospectively enrolled, the mean age was 66.5 years (range, 32 to 91). Mean time from LKN to IVtPA administration was 2.6 hours (range 0.07 to 10.8). Initial pre-IVTPA mean NIHSS was 14 (range, 3 to 26) and 24 hour mean NIHSS was 7.4, (range 0 to 30). Mean pre-IVtPA INR was 1.05 (range, 0.9 to 1.4). Mean peak post-IVtPA INR was 1.28 (range 1.01 to 3.08). Mean deviation of actual to ideal IVtPA dose was 1.02 mg (range, 22.9 to 14.4). Post IVtPA coagulopathy occurred in 6 patients (14%), with peak INR noted at a mean of 13 hours after IVtPA administration (range, 5.6 to 18.6). Five patients of the six (83%) with post IVtPA coagulopathy had low fibrinogen, and mean fibrinogen nadir was 97 mg/dL (range, 37 to 242). Post-IVtPA coagulopathy was not significantly associated with initial NIHSS, 24 hour NIHSS, LKN to IVtPA time, or deviation of actual IVtPA dose from ideal dose.Conclusion: Post-IVtpA coagulopathy occurs in 14% of patients when studied prospectively and is associated with hypofibrinogenemia, but does not appear to correlate with severity of stroke or IVtPA dosing/timing.