Our aim was to investigate body composition changes, epicardial adipose tissue thickness (EATT), serum omentin-1 levels, and the relationship among them along with some atherosclerosis markers in overt hypothyroidism. Twenty-eight newly diagnosed overt hypothyroid patients were evaluated before and after 6 months of thyroid hormone replacement therapy (THRT) and compared to the healthy subjects in this prospective longitudinal study. Body compositions were measured with dual-energy X-ray absorptiometry, and EATT was measured by echocardiography. Carotid intima-media thickness (c-IMT), flow-mediated dilatation (FMD), thyroid hormone levels, lipid parameters, high sensitive c-reactive protein, homocysteine, and omentin-1 levels were measured in all subjects. Body weight and lean body mass were higher in patients with hypothyroidism compared to euthyroid state after THRT (p = 0.012, 0.034, respectively). EATT was higher in patients with hypothyroidism than the control group (p < 0.001) and decreased with THRT (p = 0.012) but still remained higher than the control group (p < 0.001). Free T4 levels were found to be an independent factor to predict EATT (p < 0.001). In hypothyroid state, omentin-1 levels were lower than controls (p = 0.037) but increased in 6 months with THRT (p = 0.001). The c-IMT was higher, and FMD was lower in hypothyroidism compared to euthyroid state and control group (p < 0.05). Increasing lean body mass, but not adipose tissue mass, was found to be responsible for weight gain in hypothyroidism. The increased amount of EATT and decreased omentin-1 levels can contribute to the development of atherosclerosis in addition to other factors in hypothyroidism.