Background: Hemorrhagic transformation (HT) is one of the most common and severe complications in patients with acute ischemic stroke (AIS). It indicates a poor prognosis in AIS patients. However, the association of neutrophil to high-density lipoprotein ratio (NHR) with HT remains unclear. Purpose: This study examined whether the NHR has a predictive effect on HT in AIS patients and explored the predictive cutoff value of the NHR. Methods: This is a retrospective study and consecutively included AIS patients admitted to the Department of Neurology of the First Affiliated Hospital of Wannan Medical College between December 2019 and January 2022. All subjects had blood samples collected within 24 h of admission, and neutrophil counts and high-density lipoprotein counts were detected. HT was diagnosed with hemorrhage on subsequent magnetic resonance imaging (MRI) or computed tomography (CT) of the brain. Univariate logistic regression analysis was performed to identify confounding factors, and multivariate logistic regression analysis determined the correlation between NHR and HT. Receiver operating characteristic (ROC) curves were used to evaluate the clinical predictive value of NHR. Results: A total of 725 patients were finally included in this study, of which 87 (12%) developed HT. The median NHR value in the HT group was 4.31, which was significantly higher than that in the non-HT group, and the difference was statistically significant [4.31 (3.54-6.24) vs 3.63 (2.68-4.64), p < 0.001]. The binary logistic regression analysis showed that NHR was independently associated with HT in AIS patients (OR: 1.180, 95% CI: 1.036-1.344, p = 0.013). The area under ROC curve (AUC) of NHR for predicting HT in AIS patients was 0.633 (95% CI: 0.567-0.699, p < 0.001), and its optimal cutoff were 3.52. Conclusion:The NHR was a reliable and simple independent predictor of HT in AIS patients.