Aim To explore the association between serum neutrophil percentage to albumin ratio (NPAR) level and coronary artery layered plaque in patients with acute coronary syndrome (ACS). Methods 222 patients who underwent coronary angiography (CAG) and optical coherence tomography (OCT) examination of culprit vessels immediately after angiography at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from January 2018 to January 2023 and diagnosed with ACS were selected as the study subjects, and they were classified into 111 cases of layered plaque and 111 cases of non-layered plaque according to the OCT image results. Serum NPAR level was compared between the layered plaque group and the non-layered plaque group, and the influencing factors of coronary artery layered plaque were analyzed by multivariate Logistic regression analysis. Results Comparing the clinical and biochemical index data between the layered plaque group and the non-layered plaque group, the history of alcohol consumption, lumen stenosis rate, neutrophil percentage level, NPAR level was higher in the layered plaque group than that in the non-layered plaque group, and the albumin level was lower than that in the non-layered plaque group, the differences were statistically significant (P＜0.05). Comparison of the OCT characteristics showed that lipid arcs were larger and fibrous cap thickness was thinner, macrophage infiltration rate was higher, vulnerable plaques, plaque rupture, cholesterol crystals, microvessels, thrombus, calcified nodules, calcified plaques were detected at a higher rate, and fibrous plaques were detected at a lower rate in the layered plaque group, and the differences were all statistically significant (P＜0.05). Spearman correlation analysis showed that the serum NPAR a positive correlation with the rupture of plaques, and the TCFA (r＝0.436 and r＝0.622, respectively, both P＜0.05). Multivariate Logistic regression analysis showed that high level of NPAR was an independent risk factor for the development of layered plaque in culprit vessels in ACS patients (OR＝10.6,5%CI:3.242～31.999, P＜0.001). Conclusion Layered plaque is associated with plaque vulnerability characteristics, and serum NPAR level is elevated in patients with layered plaque in culprit vessels with ACS, which is an independent risk factor for coronary layered plaque in ACS patients.