Background <p>Atrial fibrillation (AF) is a common arrhythmia and the major cause of morbidity and mortality in cardiovascular disease. Although the pathogenesis of AF is unclear, insulin resistance and inflammation have been recognized to be strongly associated with AF. This study aimed to investigate the association between triglyceride-glucose (TyG) index, neutrophil to high-density lipoprotein cholesterol ratio (NHR) and AF.</p> Methods <p>A total of 1468 subjects from a single center were used in the retrospective study, and logistic regression analysis was used to determine the association between the TyG index, NHR and AF. The receiver operating characteristic (ROC) curve was used to assess the predictive ability of these independent associated with AF.</p> Results <p>AF patients exhibited higher levels of TyG index and NHR than non-AF patients. The TyG index (OR = 2.79, 95% CI 1.07–7.26, <i>P</i> = 0.029) and NHR (OR = 1.20, 95% CI 1.47–1.81, <i>P</i> &lt; 0.001) were significantly associated with AF. The TyG index and NHR remained significantly associated with AF across the subgroups analyzed and were consistent with the trend in overall outcome (<i>P</i> &lt; 0.05). ROC analysis confirmed the combination of the TyG index and NHR demonstrated moderate potential predictive ability, with improved sensitivity for the occurrence of AF (AUC = 0.762, <i>P</i> &lt; 0.001).</p> Conclusion <p>High TyG index and NHR were independently associated with AF. The combination of the TyG index and NHR showed potential predictive ability for the occurrence of AF.</p>