To investigate 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). 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 of ≥3 at 3 months. Major adverse cardiovascular events (MACE) were defined as stroke recurrence, myocardial infarction occurrence, or death. A total of 2,901 patients were enrolled and followed up for a median of 3.1 (IQR, 1.6-4.7) years. Among them, 2,643 (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 (ABID ≥0.15: OR, 1.970, 95% CI, 1.175-3.302; IAND ≥15 mmHg: OR, 1.665, 95% CI, 1.188-2.334). In Cox regression analysis, ABID ≥0.15 and IAND ≥15 mmHg were independently associated with MACE (ABID ≥0.15: HR, 1.514, 95% CI, 1.058-2.166; IAND ≥15 mmHg: HR, 1.343, 95% CI, 1.051-1.716) and all-cause mortality (ABID ≥0.15: HR, 1.524, 95% CI, 1.039-2.235; IAND ≥15 mmHg: HR, 1.516, 95% CI, 1.164-1.973) in patients without PAD. High ABID and IAND are associated with poor short-term outcome, long-term MACE occurrence, and all-cause mortality in acute ischemic stroke without PAD.