Abstract-- Objective: To evaluate the independent effect of premorbid antiplatelet use on incident ischemic stroke severity and outcome at discharge. Methods: The authors studied consecutive patients presenting within 24 hours of ischemic stroke over a 1-year period. National Institutes of Health Stroke Scale (NIHSS) score at presentation was used as index of stroke severity and a modified Rankin scale of 0 to1 at discharge as index of good functional outcome. Patients were categorized according to their premorbid antiplatelet use as antiplatelet-inclusive (AI) and no antiplatelet (NA). Demographic data, risk factors, pertinent laboratory tests, other medications, and stroke mechanisms were controlled for across the two groups using multivariate logistic regression. Results: A total of 260 individuals met study criteria: 92 patients were on antiplatelet agents prior to admission, 168 were on no antiplatelets. Pretreatment with antiplatelet was associated with lower presenting median NIHSS (4.5 vs 7, p = 0.005). Antiplatelet use was associated with less severe stroke at presentation in those having no history of stroke or TIA (4.8 vs 8.0, p = 0.03) but not in those with a prior history of stroke or TIA (4.9 vs 4.9, p = 0.987). The likelihood of a good outcome was increased in those on antiplatelets after adjusting for other variables (OR 2.105, p = 0.0073). Conclusions: Prestroke use of antiplatelet may be associated with reduced severity of incident ischemic strokes in those with no prior history of stroke or TIA, and with an increased likelihood of a good discharge outcome regardless of prior cerebrovascular event history.