To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1058 non-diabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank ≥4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 μg/ml, respectively, in diabetic women, P=0.004; 15.0 vs. 13.2 μg/ml in nondiabetic women, P=0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein and tumor necrosis factor-α receptor II. Adjustment for adiponectin did not weaken these associations, nor did adjustment for inflammatory markers attenuate the association between coffee consumption and adiponectin. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations.