Background: Rapid and accurate diagnosis and management can be lifesaving for patients with acute dyspnea. However, making a differential diagnosis and selecting early treatment for patients with acute dyspnea in the emergency setting is a clinical challenge that requires complex decision-making in order to achieve hemodynamic balance, improve functional capacity, decrease unnecessary usage of antibiotic therapy, and decrease mortality.Aim: To study the efficacy of measuring high sensitivity C-reactive protein (Hs-CRP) and procalcitonin (PCT) levels on admission in differentiating acute decompensated heart failure (ADHF) from community acquired pneumonia (CAP) in patients with acute dyspnea in the emergency setting.Methods: A comparative analytical study of ADHF and CAP patients admitted to the emergency room for acute dyspnea. Patients who qualified the criteria for both pneumonia and heart failure were excluded. Efficacy for Hs-CRP and PCT as a diagnostic markers was evaluated by using receiver operator curves (ROC). Results: Thirty patients with ADHF and 30 patients with CAP were studied. Patients with pneumonia had increased Hs-CRP and PCT levels on admission (mean walues were 76.6±41.8 mg/L, and 0.95±0.54 ng/ml respectively), compared with those with heart failure (18.53±18.49 mg/l, and 0.09±0.03 ng/ml respectively). For differentiating pneumonia from HF, the cutoff value of Hs-CRP was 15 mg/L, with sensitivity 96.7% and specificity 70%, while the cutoff value of PCT was 0.2 ng/ml with sensitivity 93.3% and specificity 100%.Conclusion: Procalcitonin and Hs-CRP levels can both independently distinguish CAP from ADHF in the emergency setting.