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Background: Clinical trials have generally showed a neutral effect of blood pressure (BP) reduction on clinical outcomes among acute ischemic stroke patients. We conducted a prespecified subgroup analysis to assess whether disease severity modifies the effect of early antihypertensive treatment on death and disability among patients with acute ischemic stroke. Methods: In the China Antihypertensive Trial in Acute Ischemic Stroke, 4,071 patients with acute ischemic stroke and elevated BP were randomly assigned to receive antihypertensive treatment or to discontinue all hypertension medications within 48 h of symptom onset. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. In this subgroup analysis, participants were categorized into 3 groups according to their baseline NIH Stroke Scale (NIHSS) scores (0-4, 5-15, or ≥ 16). Results: At 24 h after randomization, mean systolic BP differences (95% CIs) were -8.5 (-10.0 to -7.1), -9.8 (-11.4 to -8.3), and -9.1 (-14.4 to -3.8) mm Hg between the treatment and control groups (all p values <0.001) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥ 16, respectively. At day 7 after randomization, the corresponding mean systolic BP differences were -9.3 (-10.5 to -8.2), -9.1 (-10.3 to -7.8), and -10.1 (-15.1 to -5.1) mm Hg between the treatment and control groups (all p values <0.001). The primary outcome was not significantly different between the treatment and control groups at day 14 or hospital discharge among all NIHSS subgroups (p value for homogeneity = 0.66). ORs (95% CI) associated with treatment were 1.14 (0.87-1.49, p = 0.33), 1.04 (0.86-1.25, p = 0.70), and 0.67 (0.18-2.44, p = 0.54) for patients with a baseline NIHSS score of 0-4, 5-15, and ≥ 16, respectively. The composite outcome of death and major disability at 3-month follow-up did not differ between the 2 comparison groups for all NIHSS subgroups. In addition, vascular events and recurrent stroke were not significantly different between the 2 comparison groups at the 3-month follow-up visit among all NIHSS subgroups except that there was a suggestive risk reduction for recurrent stroke among those with an NIHSS score of 5-15 (OR 0.45, 95% CI 0.20-0.99, p = 0.05). Conclusion: Early BP reduction with antihypertensive medications did not reduce or increase the risk of death, major disabilities, recurrent instances of stroke, and vascular events in acute ischemic stroke patients with a variety of disease severities. [ABSTRACT FROM AUTHOR]