Irisin concentrations are decreased in subjects with overt diabetes and upregulated in those with obesity or impaired fasting glucose. However, gender-balanced data in older populations, in whom risk factors commonly culminate in overt cardiovascular disease, are scarce. We assessed in non-diabetic Caucasian subjects with stage I-II obesity in the early aging range (50 to 70 years), the relationship between irisin, body composition and markers of metabolic derangement by gender. In 60 (31 women, 29 men) non-diabetics with a body mass index ≥30 - ≤40 kg/m2, we measured anthropometrics and body composition (Air Displacement Plethysmography). We assayed lipid and glucose profile by routine methods, plasma irisin by ELISA and measured insulin resistance by the HOMA index. Irisin levels were higher in women than in men (161 [105-198]) vs 83 [33-115] ng/ml, P<0.001), and correlated directly with HOMA index in both (rho 0.735, P<0.001 M, rho 0.452, P = 0.011 F). Sex differences were maintained across insulin resistance severity stages. In men, irisin concentrations correlated directly with body mass index (rho 0.755, P<0.001), waist circumference (rho 0.623, P<0.001), fat mass index (rho 0.762, P<0.001), glucose (rho 0.408, P = 0.028), the fatty liver index (rho 0.705, P<0.001) and FINDRISC score (rho 0.536, P = 0.003). Among non-diabetic Caucasian subjects with obesity in the early stages of aging, irisin levels reflect the amount of body fat and insulin resistance severity, independently of between-gender differences in the adipomyokine concentrations and are associated with markers of visceral adiposity in men but not in women.