Inclusion Criteria:

-Ischemic stroke symptoms with onset ≤ 3 hours*.

• *or<4.5 hours according to local standard of care. Symptoms must be distinguished from another ischemic event such as syncope, seizure, migraine, and hypoglycemia. If the patient reports awakening with the event, the time of onset should be considered as last time the patient (or a witness to the patient's condition) considered herself/himself normal.

(Note: symptom onset time is determined by the timepoint at which the symptoms are known to the patient or those witnessing the patient's condition.)

• Males and females ages 18-85 years of age.
• A clot causing complete or partial occlusion (TIBI 0, 1, 2, or 3) via TCD in any one of the following areas: distal ICA, MCA (M1 or M2), PCA (P1 or P2)distal vertebral or basilar occlusions. TCD must be abnormal prior to the start of Argatroban. For patients without temporal windows (or in centers without emergent access to TCD), an abnormal CTA is required for enrollment (TIMI 0 or 1).
• Females of childbearing potential must have a negative serum pregnancy test prior to the administration of trial medication.
• Signed written informed consent by the patient or the patient's legal representative and/or guardian.
• Meet criteria for rt-PA therapy.

Exclusion Criteria:

• Evidence of intracranial hemorrhage on baseline CT scan or non-vascular cause of neurologic deficit.
• NIHSS Level of Consciousness score ≥2.
• Baseline (immediately pre-Argatroban) NIHSS ≤ 5 or patient with rapidly resolving deficit or rapidly improving symptoms consistent with TPA.
• Baseline NIHSS ≥15 for right hemisphere strokes and ≥20 for left hemisphere strokes.
• Pre-existing disability with mRS ≥ 2.
• CT scan findings of hypoattenuation of the x-ray signal (hypodensity)involving ≥ 1/2 of the MCA territory.
• Any evidence of clinically significant bleeding, or known coagulopathy.
• Patients currently on warfarin, with an elevated INR ≥ 1.5.
• Patients currently or within previous 48 hrs. on heparin with an elevated aPTT greater than the upper limit of normal.
• Heparin flush required for an IV line. Line flushes with saline only.
• History of ICH or significant bleeding episode within the 3 months before study enrollment.
• Major surgery or serious trauma within the last 6 weeks.
• Patients who have had an arterial puncture at a non-compressible site, biopsy of parenchymal organ, or lumbar puncture within the last 2 weeks.
• Previous stroke, myocardial infarction, post myocardial infarction pericarditis, intracranial surgery, or significant head trauma within 3 months of baseline.
• Uncontrolled hypertension.
• Alcohol and/or substance abuse that would increase the risk of hemorrhage in the opinion of the investigator.
• Surgical intervention anticipated within the next 7 days.
• Hepatic dysfunction, defined by liver function tests greater than 3 times upper limit of normal at baseline, specifically SGOT and SGPT.
• Abnormal blood glucose
• History of primary or metastatic brain tumor.
• Severe mental deficit prior to onset of stroke such as organic brain disorder, schizophrenia, etc.
• Concurrent severe neurologic disorder, such as seizure at onset of stroke or uncontrolled seizure disorder that complicates diagnosis of acute ischemic stroke.
• Current platelet count< 100,000/mm3.
• Life expectancy <3 months in the opinion of the investigator.
• Patients who, in the judgement of the investigator, need to be on concomitant (i.e, during the Argatroban infusion) anticoagulants other than Argatroban, including any form of heparin, UFH, LMWH, defibrinogenating agent, dextran, other direct thrombin inhibitors or thrombolytic agents, GPIIb/IIIa or warfarin.(Caveat: However, if in the judgement of the investigator a patient needs to be anticoagulated, but this can be deferred for 48 hours, then they can be included).
• Currently participating or has participated in any investigational drug or device study within 30 days before the first dose of study medication.
• Known hypersensitivity to Argatroban or its agents