Background: Although plasma adiponectin is known to have cardioprotective effects, there is limited information on the relationship between the blood adiponectin levels and left ventricular (LV) function. We sought to determine whether serum adiponectin levels have beneficial effects on LV function in a population-based cohort of middle-aged adults without known cardiovascular disease. Methods: We studied 2559 middle-aged Korean adults (1270 men and 1289 women) aged 40 to 69 years who participated in the fourth survey of the Korean Genome Epidemiology Study in 2007-2008. Serum adiponectin levels were measured, and LV function was evaluated by standard echocardiography and tissue Doppler imaging (TDI) at the mitral septal annulus. Multivariate linear regression analyses were conducted to test the independence between LV functional parameters and adiponectin after adjusting for potential confounding factors. Results: Serum adiponectin levels were higher in women (8.1 짹 5.0 ug/ml) than in men (4.9 짹 3.3 ug/ml) (P<0.001). Even though there was no significant association between serum levels of adiponectin and LV ejection function, the adiponectin levels were significantly correlated with systolic (Sa) TDI velocity in women (P=0.002) and early diastolic (Ea) TDI velocity in both men (P<0.001) and women (P<0.001) in univariate analyses. However, after adjusting for age, body mass index, systolic and diastolic blood pressures, heart rate, current smoking, current alcohol drinking, total cholesterol, triglyceride, high-sensitivity C-reactive protein, hemoglobin A1c, and homeostasis model assessment of insulin resistance, adiponectin concentration was independently associated with Sa (P=0.001) and Ea (P=0.006) TDI velocities only in women. Conclusions: In the middle-aged general population, the beneficial effects of serum adiponectin level on LV function were observed only in women. The study suggests that hypoadiponectinemia may be a risk factor for the development of overt cardiovascular disease in women.