Objective: We aimed to differentiate ischemic heart failure (HF) from non-ischemic HF in patients presenting with non-acute onset exertional dyspnea using technetium-99m methoxyisobutylisonitrile gated single photon emission tomography (Tc-99m-MIBI gSPET) imaging. Subjects and Methods: One hundred and seventy nine consecutive patients with exertional dyspnea without concomitant chest pain referred to Tc-99m-MIBI gSPET imaging were included in this study. All patients had a newly diagnosed HF with reduced ejection fraction (HFrEF). Imaging findings were compared between ischemic HF and non-ischemic HF groups. Results: Of the 179 patients, 127 had ischemic HF and 52 had non-ischemic HF. There was no difference between ischemic and non-ischemic groups in terms of age, gender, body mass index, any smoking history, diabetes mellitus, history of hypertension and hyperlipidemia. Global dysfunction of left ventricle was more common in non-ischemic HF group than ischemic HF group (82.7% vs 41.7% respectively, P<0.001). Presence of severe (3+/4+) ischemia and large perfusion defect were higher in ischemic HF group compared to non-ischemic HF group (45.7% vs 15.4%, P<0.001 and 23.6% vs 3.8%, P=0.003, respectively). Summed stress score (SSS), summed rest score and summed difference score were higher in ischemic HF group compared to non-ischemic HF group (P<0.001, P<0.001, and P=0.021, respectively). In multivariate analysis, absence of global dysfunction (P<0.001, OR=10.338, 95% CI: 3.937-27.405) and SSS (P<0.001, OR=1.208, 95% CI: 1.090-1.339) were the independent predictors of ischemic HF. Absence of global dysfunction had 58.3% sensitivity and 86.7% specificity for diagnosis of ischemic HF at gSPET imaging in patients presenting with newly diagnosed HF and exertional dyspnea without concomitant chest pain (AUC=0.705, 95% CI: 0.632-0.771, P<0.001), whereas SSS>8 had 65.4% sensitivity and 75.0% specificity (AUC=0.732, 95% CI: 0.661-0.795, P<0.001). Conclusion: Absence of global dysfunction and SSS on SPET imaging were the independent predictors of ischemic etiology of HF presenting with dyspnea without concomitant chest pain. These findings had a low sensitivity, but acceptable specificity.