Aim To investigate the relationship between serum fibroblast growth factor-21 (FGF-21), myeloperoxidase (MPO) levels and prognosis in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Methods 108 AMI patients who received PCI in our hospital from January 2016 to December 2018 were selected as the study subjects. According to whether major adverse cardiovascular events (MACE) occurred during follow-up, patients were divided into two groups:poor prognosis group (25 cases) and good prognosis group (83 cases).The levels of serum FGF-21 and MPO were detected by enzyme-linked immunosorbent assay and colloidal gold immunochromatography respectively. The relationship between FGF-21, MPO and MACE in AMI patients after PCI, and the efficacy of FGF-21, MPO in the diagnosis of MACE were analyzed. Results The levels of serum FGF-21 and MPO in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (P＜0.05). Area under ROC curve (AUC) of FGF-21＋MPO in the diagnosis of MACE in AMI patients after PCI was 0.860, which was higher than that of FGF-21 and MPO alone in the diagnosis of MACE in AMI patients after PCI. In patients with FGF-21＞140.41 ng/L and FGF-21≤140.41 ng/L, the incidence of MACE was 39.58% and 10.00%, respectively, and the difference was statistically significant (P＜0.001). In patients with MPO＞419.42 μg/L and MPO≤419.42 μg/L, the incidence of MACE was 35.00% and 8.33%, respectively, and the difference was statistically significant (P＝0.001). Cox univariate and multivariate analysis showed that FGF-21 and MPO were closely related to MACE in AMI patients after PCI (all P＜0.05). Conclusion The levels of serum FGF-21 and MPO are related to the prognosis in AMI patients after PCI, and high levels of serum FGF-21 and MPO are closely related to MACE.