OBJECTIVE: To identify the most relevant genes of cardiovascular disease in acute myocardial infarction patients using weighted gene co-expression network analysis (WGCNA). METHODS: The microarray dataset of GSE66360 was downloaded from the Gene Expression Omnibus (GEO) website. The differential genes with adjusted P < 0.05 and |log2 fold change (FC)| > 0.5 were included in the analysis. The weighed gene co-expression network analysis (WGCNA) was used to build a gene co-expression network and identify the most significant module. Cytoscape was used to filter the hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the hub genes. The key genes were defined as having high statistical and biological significance. RESULTS: A total of 4751 differentially expressed genes (DEGs) were screened from the dataset. The purple module had the highest significance in AMI. There were 47 hub genes identified from the module. The GO terms "amyloid beta protein metabolism" and "carbohydrate metabolism" and the KEGG terms "phagosome-related pathways" and "Staphylococcus aureus-associated pathways" were the pathways strongly enriched in AMI. Fatty acid translocase cluster of differentiation (CD36), formyl peptide receptor type 2 (FPR2), integrin subunit alpha M (ITGAM), and oxidized low density lipoprotein receptor 1 (OLR1) were considered key genes in AMI. CONCLUSION: Our research suggested that the underlying mechanism was related to inflammation and lipid formation. The hub genes identified were CD36, FPR2, ITGAM, and OLR1.