OBJECTIVE: To systematically analyze the factors associated with heart failure (HF) development after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). METHODS: Relevant literature on risk factors for HF following PCI in ACS patients were retrieved from PubMed, Embase, The Cochrane Library, Web of Science, and Medline buildup to September 2024. Two independent investigators conducted literature screening, quality assessment, and data extraction based on inclusion and exclusion criteria. Meta-analysis was performed using Stata 12.0 software. RESULTS: A total of 20 papers were included, comprising 45,578 patients of whom 4,345 ACS patients developed HF after PCI. Meta-analysis identified several predictors of post-PCI HF in ACS patients, including advanced age [odds ratio (OR) =1.04, 95% confidence intervals (CI): 1.03-1.06], female gender (OR=1.43, 95% CI: 1.18-1.72), history of hypertension (OR=1.54, 95% CI: 1.31-1.80), history of diabetes mellitus (OR=1.55, 95% CI: 1.39-1.72), previous myocardial infarction (OR=1.58, 95% CI: 1.11-2.23), anterior wall myocardial infarction (OR=2.22, 95% CI: 1.89-2.61), reduced left ventricular ejection fraction (LVEF) (OR=1.40, 95% CI: 1.21-1.62), elevated white blood cell count (OR=1.14, 95% CI: 1.07-1.22), atrial fibrillation [hazard ratio (HR) =2.14, 95% CI: 1.11-4.12], increased heart rate (OR=1.03, 95% CI: 1.02-1.04), elevated Pentraxin-3 (PTX3) levels (OR=2.67, 95% CI: 1.45-4.93), and decreased myocardial contractility (HR=1.18, 95% CI: 1.10-1.26). Notably, complete revascularization (HR=0.29, 95% CI: 0.10-0.86) was identified as a protective factor. Sensitivity analysis confirmed the robustness of these findings. CONCLUSIONS: Advanced age, female gender, history of hypertension and diabetes, previous myocardial infarction, anterior wall myocardial infarction, decreased LVEF at admission, increased white blood cell count, atrial fibrillation at admission, increased heart rate, elevated PTX3 levels, and impaired myocardial contractility were risk factors for HF development after PCI in ACS patients. Conversely, complete revascularization was associated with a lower risk of post-PCI HF.