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Background: The development of new-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) is a clinical complication that requires a better understanding of the causative risk factors. This study aimed to explore the risk factors and the expression and function of miR-1 and miR-133a in new atrial fibrillation after AMI. Methods: We collected clinical data from 172 patients with AMI treated with emergency percutaneous coronary intervention (PCI) between October 2021 and October 2022. Independent predictors of NOAF were determined using binary logistic univariate and multivariate regression analyses. The predictive value of NOAF was assessed using the area under the receiver operating characteristic (ROC) curve for related risk factors. In total, 172 venous blood samples were collected preoperatively and on the first day postoperatively; the expression levels of miR-1 and miR-133a were determined using the polymerase chain reaction. The clinical significance of miR-1 and miR-133a expression levels was determined by Spearman correlation analysis. Results: The Glasgow prognostic score, left atrial diameter, and infarct area were significant independent risk factors for NOAF after AMI. We observed that the expression levels of miR-1 and miR-133a were significantly higher in the NOAF group than in the non-NOAF group. On postoperative day 1, strong associations were found between miR-133a expression levels and the neutrophil ratio and between miR-1 expression levels and an increased left atrial diameter. Conclusions: Our findings indicate that the mechanism of NOAF after AMI may include an inflammatory response associated with an increased miR-1-related mechanism. Conversely, miR-133a could play a protective role in this clinical condition. [ABSTRACT FROM AUTHOR]