OBJECTIVE: This study aimed to investigate the effect of LP(a) on recurrent ischemic stroke among persons with and without diabetes, providing a basis for the precise management of patients with recurrent ischemic stroke with diabetes in clinical practice. METHODS: This study was conducted on consecutive patients with cerebral infarction diagnosed between January 2019 and March 2023 in the Second Hospital of Hebei Medical University. Stratified analyses were performed according to LP(a) level (≤/>90th percentile) and logistic regression modeling was performed to investigate the relationship between LP(a) and recurrent ischemic stroke with or without T2DM. RESULTS: In the final enrollment of 2029 patients, the number of recurrent ischemic stroke according to LP(a) >90th percentile combined with T2DM was 59.15%, which was significantly higher than in LP(a) ≤90th percentile combined with T2DM (46.17%, =0.039). After multivariate adjustment, LP(a) >90th percentile emerged as an independent risk factor for patients with T2DM (OR=2.062, 95% CI 1.218-3.489, =0.007). In patients with large artery atherosclerotic ischemic stroke, LP(a) was an independent risk factor for recurrent ischemic stroke in diabetic patients (OR=2.553, 95%CI 1.385-4.707, = 0.003), while this was not in non-diabetic patients ( = 0.228). CONCLUSION: LP(a) is an independent risk factor for recurrent ischemic stroke in the diabetic population but not in nondiabetic individuals. Simple categorization based on the presence or absence of comorbid T2DM significantly influences the association between LP(a) and recurrent ischemic stroke. Therefore, in clinical practice, for ischemic stroke patients with comorbid diabetes, the LP(a) level should be more strictly controlled.