BACKGROUND: In patients with new-onset heart failure (HF), invasive coronary angiography (ICA) is recommended to rule out coronary artery disease (CAD). OBJECTIVE: To investigate the utility of a coronary artery calcium score (CACS) and coronary computed tomography angiography (CCTA) for rule-out of obstructive CAD in patients with new-onset HF. METHODS AND RESULTS: Patients with new-onset HF referred for cardiac computed tomography (CT) were included (2008-2022). Patients were grouped according to CACS and CCTA findings. Stenosis on CCTA was defined as ≥1 vessel with ≥50% luminal diameter stenosis. Obstructive CAD was defined as ≥1 vessel with ≥50% luminal diameter stenosis at ICA performed within 120 days from cardiac CT. Revascularization procedures within 120 days from cardiac CT were identified.Overall, 3336 patients were eligible. Obstructive CAD was ruled out in 2332/2780 patients (83.8%) with complete cardiac CT. 1032 (30.9%) patients had CACS=0 and 377 (11.3%) patients had CACS≥1000.18.0% of patients had stenosis on CCTA, ranging from 2.8% to 71.7% in patients with CACS=0 and CACS≥1000, respectively.Obstructive CAD at second-line ICA was diagnosed in 11.5% of patients, ranging from 1.2% to 47.2% in patients with CACS=0 and CACS≥1000, respectively. Revascularization was performed in 6.9% of patients, ranging from 0.6% to 26.5% in patients with CACS=0 and CACS≥1000, respectively. CONCLUSION: In stable patients with new-onset HF, cardiac CT may be considered as the primary imaging modality to rule out ischemic heart disease, and implementation of a CT-based strategy for ischemia rule-out may substantially reduce the need for invasive examination.