Carbohydrate antigen 125 (CA125) has long been used as an ovarian cancer biomarker. However, because it is not specific for ovarian cells, CA125 could also be used to monitor congestion and inflammation in heart disease. Acute heart failure (HF) is used to identify patients with a worse prognosis in ST-segment elevation myocardial infarction (STEMI). We aimed to determine the association of CA125 with acute HF in STEMI and to compare CA125 with N-terminal pro brain natriuretic peptide (NTproBNP) with a cross-sectional study. At admission, patients were examined to define Killip class and then underwent coronary angioplasty. Blood samples, preferably taken in the hemodynamic ward, were centrifuged (1500 g for 15 min at ambient temperature) and stored at -80°C until biomarker assays were performed. Patients were divided into two groups according to the presence or absence of congestion. Patients in Killip class ≥II were in the congestion group and those with Killip <II in the absence of congestion group. We evaluated 231 patients. The mean age was 63.3 years. HF at admission was identified in 17.7% of patients. CA125 and NTproBNP levels were higher in patients with Killip class ≥II than those with Killip class <II (8.03 vs 9.17, P=0.016 and 772.45 vs 1925, P=0.007, respectively). The area under the receiver operator characteristic curve was 0.60 (95%CI 0.53-0.66, P=0.024) for CA125 and 0.63 (95%CI 0.56-0.69, P=0.001) for NTproBNP. There was no statistical difference between the curves (P=0.69). CA125 has similar use to NTproBNP in identifying acute HF in patients presenting with STEMI.