Background: The optimal timing for initiating antihypertensive therapy after acute ischemic stroke (AIS), particularly regarding cognitive outcomes, remains uncertain. This study investigated the association between treatment timing and 3-month cognitive function. Methods: This prespecified analysis of the China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) included patients completing 3-month Montreal Cognitive Assessment (MoCA). Participants were randomized to early (immediate) or delayed (day 8) antihypertensive treatment, with MoCA score as primary outcome. Results: A total of 1,682 patients completed the cognitive assessment; 823 received early antihypertensive treatment and 859 received delayed treatment. Baseline characteristics were comparable between the two groups. The median MoCA score was 23 in both groups (β, -0.06; 95% CI, -0.16–0·03; P = 0.19). Additionally, the proportion of individuals with MoCA scores <25 was similar between the two groups (62% vs 59%; OR, 1.15; 95% CI, 0.95-1.40; P = 0.16). Exploratory subgroup analyses suggested a potential interaction by prior antihypertensive use, whereby early antihypertensive treatment was associated with worse cognitive outcomes in patients with prior antihypertensive use (OR,1.34; 95%CI ,1.01-1.77; P =0.03; P for interaction = 0.04). Conclusions: Early antihypertensive initiation did not improve 3-month cognitive outcomes in AIS patients, highlighting the importance of individualized therapy, especially for high-risk PSCI subgroups.