Background: This study investigated the association of high ankle-brachial index difference (ABID) and systolic inter-ankle blood pressure difference (IAND) with short- and long-term outcomes in acute ischemic stroke patients without peripheral artery disease (PAD). Methods: Consecutive patients with acute ischemic stroke who underwent ankle-brachial index (ABI) measurement were enrolled. ABID was calculated as |right ABI-left ABI|. IAND and systolic inter-arm blood pressure difference (IAD) were calculated as |right systolic blood pressure – left systolic blood pressure|. Poor functional outcome was defined as modified Rankin Scale score ≥3 at 3 months. Major adverse cardiovascular events (MACEs) were defined as stroke recurrence, myocardial infarction, or death. Results: A total of 2901 patients were enrolled and followed up for a median of 3.1 (interquartile range, 1.6–4.7) years. Among them, 2643 (84.9%) patients did not have PAD. In the logistic regression analysis, ABID ≥ 0.15 and IAND ≥ 15 mmHg were independently associated with poor functional outcome (odds ratio (OR), 1.970, 95% confidence interval (CI), 1.175‒3.302; OR, 1.665, 95% CI, 1.188‒2.334, respectively). In Cox regression analysis, ABID ≥0.15 and IAND ≥ 15 mmHg were independently associated with MACEs (hazard ratio (HR), 1.514, 95% CI, 1.058‒2.166; HR, 1.343, 95% CI, 1.051‒1.716, respectively) and all-cause mortality (HR, 1.524, 95% CI, 1.039‒2.235; HR, 1.516, 95% CI, 1.164‒1.973, respectively) in patients without PAD. Conclusion: High ABID and IAND are associated with poor short-term outcomes, long-term MACE occurrence, and all-cause mortality in acute ischemic stroke without PAD.