OBJECTIVE Acute decompensated heart failure (ADHF) caused by ischemic heart disease is associated with higher mortality and requires immediate diagnosis. Recently, novel methods to diagnose non-ST elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin have been applied. We compared the clinical utility of high-sensitivity troponin I (hS-TnI), delta troponin I, and other traditional methods to diagnose NSTEMI in patients with ADHF. METHODS This retrospective cross-sectional study was conducted to analyze patients with ADHF who underwent hS-TnI evaluation of 0-2-h protocol in our emergency department. Patients were grouped according to a diagnosis of NSTEMI. RESULTS A total of 524 ADHF [ADHF with NSTEMI, n=109 (20.8%)] patients were enrolled in this analysis. The mean values of hS-TnI (ng/mL) in the ADHF with and without NSTEMI groups were 2.44±5.60 and 0.25±0.91, respectively. Multivariable analysis revealed that regional wall-motion abnormality, T-wave inversion/hyperacute T wave, and initial and delta hS-TnI were predictive factors for NSTEMI. Laboratory values related to cardiac biomarkers, including hS-TnI [odds ratio (OR) (95% confidence interval, CI): 2.18], and the delta hS-TnI [OR (95% CI): 1.55] were significant predictors of NSTEMI. Moreover, receiver operating characteristic analysis showed that the areas under receiver operating characteristic curves for electrocardiographic abnormalities, initial hS-TnI, and delta hS-TnI were 0.794, 0.802, and 0.773, respectively. CONCLUSIONS For diagnosis of suspected NSTEMI in patients with ADHF, initial hS-TnI assay has similar predictive value as ischemic changes on electrocardiogram and superior predictive value than delta hS-TnI calculated by the 0-2-h protocol.