Secondary Prevention of Small Subcortical Strokes Trial

INCLUSION: Small subcortical ischemic stroke or subcortical TIA. Inclusion criteria are based on TOAST criteria supplemented by required MRI data. All of the following criteria must be met: * One of the lacunar stroke clinical syndromes (adapted from Fisher) lasting \> 24 hrs within the past 6 months * Absence of signs or symptoms of cortical dysfunction such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect, etc. * No ipsilateral cervical carotid stenosis (≥50%) by a reliable imaging modality done in an approved laboratory since the qualifying small subcortical stroke (S3), if hemispheric. * No major-risk cardioembolic sources requiring anticoagulation or other specific therapy. Minor-risk cardioembolic sources will be permitted if anticoagulation is not prescribed by the patient's primary care physician. * Subcortical TIA with corresponding lesion on DWI. * MRI evidence of S3: a. Presence of an S3 (1.5 and 2 cm in diameter corresponding to the qualifying event on DWI; when TIA, ADC image must confirm lesion or T2/FLAIR (hyperintense lesions) (required for all brainstem events) OR multiple S3s on FLAIR/TI(\<1.5 cm in diameter) (hypointense lesions) b. Absence of cortical stroke and large subcortical stroke (recent or remote). EXCLUSION: To be eligible for entry into the study, the patient must not meet any of the criteria listed below: * Disabling stroke (Modified Rankin Scale less than or equal to 4) * Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke * Age under 30 years * High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc) * Anticipated requirement for long-term use of anticoagulants (e.g. recurrent DVT) or other antiplatelets * Prior cortical stroke (diagnosed either clinically or by neuroimaging), or prior cortical or retinal TIA * Prior ipsilateral carotid endarterectomy * Impaired renal function: GFR \<40 * Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR) * A score \< 24 (adjusted for age and education) on the Folstein Mini Mental Status Examination * Medical contraindication to MRI * Pregnancy or women of child-bearing potential who are not following an effective method of contraception * Geographic or social factors making study participation impractical * Unable or unwilling to provide informed consent * Unlikely to be compliant with therapy/unwilling to return for frequent clinic visits * Patients concurrently participating in another study with an investigational drug or device * Other likely specific cause of stroke (e.g. dissection, vasculitis, prothrombotic diathesis, drug abuse)