While high-sensitivity troponin-T (hsTnT) and C-reactive protein (hsCRP) are associated with structural heart disease, we thought to determine whether biomarkers can predict which heart is healthy based on multimodality imaging. Patients from the emergency department with acute chest pain suggestive of acute coronary syndrome undergoing contrast enhanced cardiac CT and stress single photon emission computed tomography (SPECT) myocardial perfusion imaging were included. HsTnT and hsCRP were assessed at time of CT. Imaging data were assessed for coronary atherosclerosis, left ventricular hypertrophy/dysfunction and myocardial perfusion abnormalities. Patients were stratified into those with or without any cardiac findings, who were considered as cardiac healthy. For biomarkers, low cut-off corresponding to good specificity and high cut-off corresponding to good sensitivity for cardiac health were derived. Among 117 patients (52 years, 55 % male), 42 (36 %) were cardiac healthy based on cardiac CT and SPECT imaging. These patients had significantly lower hsTnT and hsCRP levels as compared to those with functional or structural abnormalities (3.58 vs. 5.63 ng/L, p = 0.002; 0.82 vs. 1.93 mg/L, p = 0.0005; respectively). Patients with both low hsTnT (<3.00 ng/L) and hsCRP (<0.45 mg/L) had a probability of 85 % for being cardiac healthy. In contrast, patients with high hsTnT (>7.00 ng/L) and hsCRP (>2.00 mg/L) had 8 % probability for being cardiac healthy. Discriminative capacity of a dual-biomarker strategy was significantly improved as compared to hsTnT or hsCRP alone or to Framingham Risk score (AUC: 0.781 vs. 0.691; vs. 0.678; vs. 0.649; all p ≤ 0.02, respectively). A dual-biomarker strategy of hsTnT and hsCRP is highly discriminative for patients with normal cardiac structure and function and provides incremental value beyond the Framingham risk score.