Objective To explore the predictive value of serum pentraxin 3 (PTX3), galectin-3 (Gal-3) and homocysteine (Hcy) for new-onset atrial fibrillation in patients with acute myocardial infarction (AMI).Methods A total of 261 patients with AMI admitted to the First People's Hospital of Chuzhou from January 2021 to December 2024 were retrospectively selected. The enzyme-linked immunosorbent assay was conducted to measure serum PTX3, Gal-3 and Hcy levels. The patients were divided into the occurrence group (52 cases) and the non-occurrence group (209 cases) according to whether new-onset atrial fibrillation occurred during hospitalization. The clinical characteristics were compared between the two groups, and multivariable Logistic regression analysis was performed to analyze the independent factors affecting new-onset atrial fibrillation. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of PTX3, Gal-3 and Hcy for new-onset atrial fibrillation.Results The age, heart rate, left atrial diameter (LAD), and PTX3, Gal-3 and Hcy levels in the occurrence group were higher than those in the non-occurrence group, and the left ventricular ejection fraction (LVEF) in the occurrence group was lower than that in the non-occurrence group (P < 0.05). The multivariable Logistic regression analysis revealed that older age [O^R = 1.441 (95% CI: 1.091, 1.903) ], higher heart rate [O^R = 1.267 (95% CI: 1.068, 1.503) ], lower LVEF levels [O^R = 0.426 (95% CI: 0.262, 0.681) ], higher PTX3 levels [O^R = 2.816 (95% CI: 1.567, 4.376) ], higher Gal-3 levels [O^R = 4.302 (95% CI: 1.685, 4.705) ], and higher Hcy levels [O^R = 4.528 (95% CI: 2.087, 8.866) ] were all risk factors for new-onset atrial fibrillation in AMI patients (P < 0.05). The ROC curve analysis showed that the sensitivities of serum PTX3, Gal-3, Hcy and the combination of the three for predicting new-onset atrial fibrillation in AMI patients were 70.30%, 73.00%, 78.40% and 89.20%, with the specificities being 69.10%, 68.50%, 73.20% and 81.90%, and the areas under the curves being 0.791, 0.795, 0.834, and 0.926, respectively (P < 0.05).Conclusion PTX3, Gal-3 and Hcy are independent risk factors for new-onset atrial fibrillation in patients with AMI, and their levels have certain predictive value for the occurrence of new-onset atrial fibrillation.