ObjectiveWe investigated whether interankle blood pressure difference (IAND) can predict major adverse cardiovascular events (MACEs) in patients with cryptogenic stroke (CS) without peripheral artery disease (PAD).DesignA retrospective cohort study.SettingRetrospective medical record data of patients with first-ever acute cerebral infarction who were admitted between 1 January 2007 and 31 July 2013.ParticipantsCS patients admitted within 7 days of symptom onset were included.Outcome measuresMACEs were defined as stroke recurrence, myocardial infarction occurrence, or death. Survival analyses were conducted using the Kaplan-Meier method and Cox regression analysis.MethodsConsecutive CS patients without PAD who underwent ankle–brachial index (ABI) measurements were enrolled. PAD was defined if a patient had an ABI of <0.90 or a history of angiographically confirmed PAD. Systolic and diastolic IANDs were calculated as follows: right ankle blood pressure—left ankle blood pressure.ResultsA total of 612 patients were enrolled and followed up for a median 2.6 (interquartile range, 1.0–4.3) years. In the Cox regression analysis, systolic and diastolic IANDs ≥15 mm Hg were independently associated with MACEs in CS patients without PAD (hazard ratio (HR) 2.115, 95% confidence interval (CI) 1.230 to 3.635 and HR 2.523, 95% CI 1.086 to 5.863, respectively). In the subgroup analysis, systolic IAND ≥15 mm Hg was independently associated with MACEs in older patients (age ≥65 years) (HR 2.242, 95% CI 1.170 to 4.298) but not in younger patients (age <65 years).ConclusionsLarge IAND is independently associated with the long-term occurrence of MACEs in patients with CS without PAD. In particular, the association between IAND and MACEs is only valid in elderly patients.