Smoking is the leading cause of preventable death. Epicardial adipose tissue (EAT) surrounds the heart surface and creates local and systemic effects secreting the hormones, cytokines, inflammatory mediators. Previous studies demonstrated that both smoking and EAT have a strong association with inflammation and atherosclerosis.Our study aimed to determine the relationship of smoking with EAT thickness and inflammation by evaluating smokers and non-smokers. A total of 259 healthy male and female participants between the ages of 18-65, without a history of chronic disease and with a body mass index within normal limits, were included in a study. EAT thickness measurements were made by transthoracic echocardiography and EAT thicknesses of smokers and non-smokers were compared. In addition, the effects of smoking and EAT thickness on different inflammatory parameters were evaluated. When the EAT thicknesses were compared between smokers and non-smokers (2.60±1.2), a statistically significant difference was found in favor of smokers (3.84±1.84) (p<0.001). A moderate positive correlation was found among age, body mass index, smoking duration in years, pack/year and EAT thickness. The difference among waist circumference, the number of cigarettes smoked daily, diastolic blood pressure, fasting blood glucose, ALT, AST, total cholesterol, triglyceride, LDL-cholesterol, CRP, uric acid, platelet count, MPV values, platelet/lymphocyte ratio and EAT thickness were found meaningful, but the weak correlation in different ratios were determined. Smoking was found to be the most important determinant of EAT thickness. Other determinants of EAT thickness were age, body mass index, CRP and female gender. The significant statistical relationship between smoking and EAT thickness suggests that smoking increases EAT thickness and inflammatory parameters. Co-assessment of the EAT and blood inflammatory parameters in smokers may guide the initiation of medical treatment in primary prevention or other therapies.