Objective: Exploring novel relevant factors associated with recurrent ischemic stroke. Methods: This is a retrospective study, patients were divided into first-ever ischemic stroke group and recurrent ischemic stroke groups. We conducted a comparative analysis of baseline data between the two groups. Multifactorial logistic regression analysis was performed to identify factors associated with recurrent ischemic stroke. Grouped according to butyryl cholinesterase levels, to elucidate the relationship between butyryl cholinesterase levels and stroke recurrence. Results: A total of 2029 patients were included, with 1174 in the first-ever ischemic stroke group and 855 in the recurrent ischemic stroke group. Age, hypertension, diabetes, alanine aminotransferase, and lipoprotein(a) were identified as risk factors for recurrent ischemic stroke (ALL p< 0.05). Erythrocyte count, butyryl cholinesterase, low-density lipoprotein, and non-atherosclerotic type of large arteries were found to be negative associated with recurrent ischemic stroke (ALL p< 0.05). Subgroup analyses indicated that butyryl cholinesterase levels were significantly negatively associated with recurrent ischemic stroke in males (OR=0.814, p< 0.001, 95% CI: 0.761 similar to 0.871), especially under 60 years (OR=0.781, p< 0.001, 95% CI: 0.708 similar to 0.862). After adjusting for multifactorial regression analyses, the recurrent rate in the lowest quartile of butyryl cholinesterase levels was 2.281 times that of the highest quartile (OR=2.281, p< 0.05, 95% CI: 1.318 similar to 3.948). Conclusion: Age, hypertension, diabetes, alanine aminotransferase, and lipoprotein(a) are independent risk factors for the recurrence of ischemic stroke. The inverse association between butyryl cholinesterase levels and stroke recurrence suggests butyryl cholinesterase may serve as a potential target for therapeutic intervention to improve the prognosis of ischemic stroke.