Aim To investigate the relationship between serum microRNA-26a-5p (miR-26a-5p) level and heart failure (HF) in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). Methods 223 patients with STEMI in our hospital from February to October 2018 were selected as the study objects. According to whether patients with STEMI complicated with HF after PCI, they were divided into HF group (n＝56) and non-HF group (n＝167). The level of miR-26a-5p in peripheral blood of patients with STEMI was detected by real-time fluorescent quantitative PCR. The clinical data and miR-26a-5p levels were compared between the two groups. The predictive value of miR-26a-5p for HF after PCI in STEMI patients was evaluated by ROC curve. Results The age, diabetes history, acute anterior wall STEMI and the time from onset to treatment in HF group were higher than those in non-HF group (P＜0.05). There were time effect, inter group effect and interaction effect in the comparison of miR-26a-5p levels before PCI, 1 day and 7 days after PCI between the two groups (P＜0.001). The area under ROC curve of miR-26a-5p level 7 days after PCI for evaluating STEMI patients complicated with HF was higher than that before PCI and 1 day after PCI (P＜0.001). Logistic regression analysis showed that age, lesion type, time from onset to treatment, and miR-26a-5p level 7 days after PCI were closely related to STEMI patients with HF (P＜0.05). Conclusions miR-26a-5p is closely related to HF after PCI in STEMI patients. The detection of miR-26a-5p level 7 days after PCI can help to predict the occurrence of HF.