The relation of orthostatic blood pressure decrease, or increase, with occurrence of ischemic stroke subtypes has not been examined. We investigated the association of orthostatic blood pressure change (within 2 minutes after supine to standing) obtained at baseline (1987 to 1989) in the Atherosclerosis Risk in Communities Study with incidence of ischemic stroke subtypes through 2007. Among 12 817 black and white individuals without a history of stroke at baseline, 680 ischemic strokes (153 lacunar, 383 nonlacunar thrombotic, and 144 cardioembolic strokes) occurred during a median follow-up of 18.7 years. There was a U-shaped association between orthostatic systolic blood pressure change and lacunar stroke incidence (quadratic P=0.004). In contrast, orthostatic systolic blood pressure decrease of 20 mm Hg or more was associated with increased occurrence of nonlacunar thrombotic and cardioembolic strokes independent of sitting systolic blood pressure, antihypertensive medication use, diabetes, and other lifestyle, physiological, biochemical, and medical conditions at baseline (for nonlacunar thrombotic: hazard ratio, 2.02; 95% CI, 1.43 to 2.84; for cardioembolic: hazard ratio, 1.85, 95% CI, 1.01 to 3.39). Orthostatic diastolic blood pressure decrease was associated with increased risk of nonlacunar thrombotic and cardioembolic strokes; the hazard ratios (95% CI) associated with 10 mm Hg lower orthostatic diastolic blood pressure (continuous) were 1.26 (1.06 to 1.50) and 1.41 (1.06 to 1.88), respectively, in fully adjusted models. In conclusion, the present study found that nonlacunar ischemic stroke incidence was positively associated with an orthostatic decrease of systolic and diastolic blood pressure, whereas greater lacunar stroke incidence was associated with both orthostatic increases and decreases in systolic blood pressure.