Chest pain is a clinical problem which often results in emergency department visits and is characterized by difficult differential diagnosis. Although many investigations can be used in the differential diagnosis of chest pain symptoms, it is forcing emergency physicians. Copeptin (CPP), is a 39-amino acid glycosylated peptide and a potential new serum inflammation marker. In this study, we aimed to investigate use of copeptin in differential diagnosis of fatal chest pain. This study included 150 patients presenting with chest pain at the emergency department over 1 year. The causes of life-threatening chest pain included aortic dissection, pulmonary thromboembolism, and acute myocardial infarction (MI); there were 90 patients in this category, identified as Group 1. Meanwhile, there were 60 patients with non-life-threatening, non-specific causes of chest pain, who were categorized in Group 2. As a Control Group, 30 healthy individuals with normal physical examination results were included. In terms of blood copeptin levels, the result was 0.48 ± 0.27 ng/ml for the Control Group, 1.03 ± 0.56 ng/ml for Group 1, and 0.50 ± 0.32 ng/ml for Group 2. There was a statistically significant difference between Group 1 and Group 2 (p<0.05), while no significant difference was found between Group 2 and the Control Group (p>0.05). Serum copeptin value should be used in differential diagnosis of fatal chest pain.