Background: Leptin is a bioactive substance secreted by adipose tissue and exerts pleiotropic actions on glucose metabolism. It may promote atherosclerosis and increase cardiovascular events. Objective: The aim of this study was to determine the role of leptin as a risk factor in non-obese patients presented with acute coronary syndrome and its relation to midterm prognosis. Patients and Methods: The study included 60 non-obese patients who were presented to Coronary Care Unit (CCU) of Ain Shams University Hospital with acute coronary syndrome (ACS). Patients were classified into 3 Groups. Group A was composed of 30 patients presented with ST-segment elevation myocardial infarction (STEMI), Group B included 15 patients presented with non-ST segment elevation myocardial infarction (NSTEMI) and Group C included 15 patients presented with unstable angina. The study also included control group composed of 20 healthy non-obese subjects who gave no history of chest pain or symptoms suggestive of coronary artery disease (CAD). Results: Mean serum leptin level in all patients was significantly higher compared to control group. As regards complications; mean serum leptin level was higher in patients with adverse outcome compared to other patients. Conclusion: The concentration of leptin is positively correlated with ACS. The mean value of serum leptin in all patients was significantly higher compared to control. The study suggests that leptin is a significant cardiovascular risk factor for ACS independent of traditional cardiovascular risk factors. Serum leptin may be a useful marker in risk stratification of ACS.