Heart failure (HF) secondary to acute myocardial infarction (AMI) is a public health concern. The current study aimed to investigate differentially expressed genes (DEGs) and their possible function in HF post-myocardial infarction. The GSE59867 dataset included microarray data from peripheral blood samples obtained from HF and non-HF patients following AMI at 4 time points (admission, discharge, and 1 and 6 months post-AMI). Time-series DEGs were analyzed using R Bioconductor. Functional enrichment analysis was performed, followed by analysis of protein-protein interactions (PPIs). A total of 108 DEGs on admission, 32 DEGs on discharge, 41 DEGs at 1 month post-AMI and 19 DEGs at 6 months post-AMI were identified. Among these DEGs, 4 genes were downregulated at all the 4 time points. These included fatty acid desaturase 2, leucine rich repeat neuronal protein 3, G-protein coupled receptor 15 and adenylate kinase 5. Functional enrichment analysis revealed that these DEGs were mainly enriched in ‘inflammatory response’, ‘immune response’, ‘toll-like receptor signaling pathway’ and ‘NF-κβ signaling pathway’. Furthermore, PPI network analysis revealed that C-X-C motif chemokine ligand 8 and interleukin 1β were hub genes. The current study identified candidate DEGs and pathways that may serve important roles in the development of HF following AMI. The results obtained in the current study may guide the development of novel therapeutic agents for HF following AMI.