Background: Nesfatin, as an adipokine, has been shown to have a number of metabolic effects associated with a variety of inflammatory diseases. The current study aimed at investigating the relationship of nesfatin-1 levels with biochemical, echocardiographic, and angiographic findings, especially with the epicardial fat thickness (EFT) in patients with coronary artery disease. Methods: This cross-sectional study was conducted on 90 patients who were candidates for angiography. The patients were then divided into one control group (with normal angiography but a history of chest pain; n=30), as well as stable-AP (with a diagnosis of stable angina pectoris; n=30) and acute-MI groups (with a diagnosis of acute myocardial infarction; n=30). Demographic, biochemical, angiographic, and echocardiographic parameters of all subjects were evaluated in this study. Results: Serum levels of nesfatin-1 in acute-MI and stable-AP groups were significantly reduced, compared to the healthy subjects (P<0.001 and P<0.01, respectively); however, there was no significant difference between acute-MI and stable-AP groups. In addition, the findings demonstrated a negative relationship of nesfatin-1 with low-density lipoprotein, Gensini score, white blood cell, troponin T, EFT, and creatine kinase-MB (CK-MB). However, there was a positive association between nesfatin-1 and left ventricle ejection fraction (%). Conclusion: Decreased levels of nesfatin-1 in acute-MI and stable-AP groups as well as its association with several parameters, such as EFT, CK-MB, and Gensini score, may indicate the potential role of nesfatin-1 in the process of atherosclerosis, which requires further studies.