Background Acute myocardial infarction (AMI) and postmyocardial infarction heart failure (pMIHF) have high mortality rates worldwide. This study aimed to explore lipidomic profiles and identify potential biomarkers for the prediction of death and heart failure (HF) after AMI. Methods All serum samples were collected at Xuanwu Hospital, Capital Medical University, and their clinical characteristics and lipidomic profiles were analyzed in different groups. LC-MS/MS was used for lipidomic analyses, and underlying biomarkers were screened by receiver operating characteristic (ROC) curve analysis. Results Lipidomic analyses of the survival and nonsurvival groups revealed that the decrease of the content of SM (d18:1/22:0), PE (P-20:1/18:0), PC (18:2), LPE (18:2), PE (P-20:0/18:0), LPC (18:0) and PC (20:0/20:3) while increase of the content of PG (18:1/18:1) could increase the risk of death after AMI. In parallel, the lipidomic analysis of the HF and non-HF groups revealed that the decrease of the content of PC (20:3/20:4), LPC (20:3), LPC (18:0), LPC (18:2), LPC (20:0), LPC (18:3), LPE (16:1) and PC (18:2/20:3) could increase the risk of HF after AMI. Conclusion Several lipids could be potential biomarkers for the prediction of death and HF after AMI.Copyright © 2024. Published by Elsevier B.V.