Diastolic dysfunction (DD) with preserved left ventricular (LV) ejection fraction (EF) has been linked to obesity. Adiponectin is a cytokine related to obesity and obesity-linked cardiovascular complications. The authors aimed to determine the independent association of DD with adiponectin. Fifty patients with impaired relaxation DD and a normal EF and age-matched normal controls were recruited. Plasma levels of total and high molecular weight (HMW) adiponectin were measured. Mid and low molecular weight (MMW+LMW) fractions of adiponectin were calculated by subtracting HMW fraction from total adiponectin. The DD group had significantly lower total (median, 4.4 vs 12.7μg/mL; P=001), HMW fraction (median, 1.3 vs 3.4μg/mL; P=02), and MMW+LMW fraction of adiponectin (median, 3.8 vs 7.2 μg/mL; P=01). Body mass index (BMI) negatively correlated with total (r:-0.46, P=003), HMW (r:-0.32, P=038), and MMW+LMW (r:-0.40, P=006) fractions of adiponectin. DD had an independent association with both BMI (P<05) and total adiponectin (P<001) in linear regression model using sex, BMI, blood pressure, and total adiponectin as covariates. DD was associated with BMI (P=02), HMW fraction (P=03), and MMW+LMW fraction (P=004) in similar linear regression analyses. Adiponectin deficiency may be one explanation for the adiposity-related cardiac oxidation known to be involved in the pathogenesis of DD.