Objective: To analyze the correlation between plasma exosomal miR-409-3p and perioperative neurocognitive disorders (PND) after coronary artery bypass grafting. Methods: A total of 76 patients undergoing coronary artery bypass graft surgery were enrolled in this study. Neuropsychological test assessments were performed 1 day before and 7 days after surgery, and the patients were divided into PND group (n=24 cases) and non-PND group according to the evaluation results (n=52 cases). The plasma exosomes of all patients were collected and extracted, and they were identified by transmission electron microscopy, particle size analysis, and western blot. qRT-PCR was used to detect the expression level of exosomal miR-409-3p. Logistic regression analysis was used to evaluate the risk factors for PND. Results: There were 24 cases of PND and 52 cases of non-PND. There were statistical differences in age, operation time and education years. The expression of plasma exosomal miR-409-3p in PND patients was higher than that in non-PND patients. Age, operation time, and plasma exosomal miR-409-3p were independent risk factors for PND. Conclusion: The highly expressed plasma exosomal miR-409-3p can be used as a new molecular marker for PND in patients undergoing coronary artery bypass graft surgery.