Objective To compare the predictive value of combined biochemical markers and left ventricular longitudinal layer-specific strain for major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).Methods In this prospective study, 151 ACS patients who underwent their first PCI at Anshun People''s Hospital between September 2022 and October 2023 were selected. Patients were grouped based on whether they experienced MACE within one year post-discharge: 36 in the MACE group and 115 in the non-MACE group. Preoperative biochemical markers were collected, and two-dimensional speckle tracking imaging (2D-STI) was used to analyze global longitudinal strain (GLS) of the left ventricular endocardium (GLSendo), mid-myocardium (GLSmid), and epicardium (GLSepi), as well as the transmural strain gradient (ΔGLS). Differences in these parameters between the two groups were compared, and binary logistic regression was used to analyze factors influencing MACE occurrence. The predictive value of different biochemical markers, myocardial layer-specific longitudinal strain parameters, and their combination for MACE occurrence after PCI in ACS patients was evaluated using ROC curves.Results Compared to the non-MACE group, the MACE group had significantly higher NT-proBNP and hs-CRP levels, while GLSendo, GLSmid, GLSepi, and ΔGLS were significantly lower (P < 0.01). Binary logistic regression analysis showed that NT-proBNP, hs-CRP, and GLSendo were independent predictors of MACE after PCI in ACS patients (P < 0.05). The areas under the ROC curve (AUC) for predicting MACE with NT-proBNP, hs-CRP, GLSendo alone, GLSendo combined with NT-proBNP and hs-CRP were 0.684 (0.584–0.783), 0.705 (0.611–0.799), 0.787 (0.719–0.914), 0.835 (0.743–0.926) and 0.841 (0.749–0.933), The combined prediction of GLSendo, NT-proBNP, and hs-CRP for MACE occurrence after PCI in ACS patients resulted in an AUC of 0.855 (0.769–0.941).Conclusions NT-proBNP, hs-CRP, and GLSendo can each predict the occurrence of MACE after PCI in ACS patients, with the best predictive performance achieved when the three are combined. 【Keywords】 Two-dimensional speckle tracking layer-specific strain; adverse cardiovascular events; acute coronary syndrome; combined prediction.