Objective To investigate the clinical value of cardiac troponin T (cTnT) , cystatin C (CysC) combined with N-terminal pro-B type brain natriuretic peptide (NT-proBNP) in the diagnosis of heart failure. Methods 52 patients with heart failure admitted to Hebi Municipal Hospital of Traditional Chinese Medicine were selected as the observation group and 50 healthy subjects as the control group. The inclusion time was from December 2022 to July 2024. cTnT, CysC and NT-proBNP were detected in all patients. To analyze the diagnostic efficacy of cTnT and CysC combined with NT-proBNP in heart failure. Results The NT-proBNP (0.38 ± 0.10) ng/mL, CysC (2.13 ± 0.34) mg/L, and cTnT (2487.85 ± 64.31) ng/L in the observation group were significantly higher than those in the control group (0.07 ± 0.02) ng/mL, (0.84 ± 0.12) mg/L, and (46.83 ± 11.24) ng/L (P<0.05). The results of cTnT and CysC combined with NT-proBNP were consistent with those of cardiac color ultrasound (Kappa=0.823, P<0.001). The positive predictive value, negative predictive value, sensitivity, specificity and accuracy of cTnT and CysC combined with NT-proBNP were 96.15%, 86.00%, 87.72%, 95.56% and 91.18%, respectively. Conclusion cTnT, CysC combined with NT-proBNP have high diagnostic efficacy in patients with heart failure, and has important clinical application value for early recognition and disease evaluation of patients with heart failure.