Previous studies suggested that the adipocytokines, adiponectin and leptin, are associated with the progression and prognosis of coronary artery disease (CAD). The aim of this study was to differentially evaluate plasma levels of adiponectin and leptin in patients with CAD and their association with conventional laboratory parameters and markers of platelet activation. We consecutively evaluated 220 patients, who presented with a symptomatic CAD. Among these 83 (37.7%) presented with an acute coronary syndrome (ACS) and 137 (62.3%) with a stable angina pectoris (SAP). All patients have received coronary angiography. Baseline concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Lower detection limits of the assay were 0.079 ng/mL for total adiponectin and 15.6 pg/mL for leptin. Patients with ACS showed significantly enhanced plasma levels of adiponectin and leptin compared with SAP (ACS vs. SAP (mean +/- SD): adiponectin: 9.9 +/- 7.6 microg/mL vs. 7.2 +/- 5.7 microg/mL; P = 0.008; leptin: 20.9 +/- 16.4 ng/mL vs. 15.2 +/- 10.9 ng/mL; P = 0.012). However, a correlation between plasma total adiponectin and leptin levels has not been observed (r = 0.038; P = 0.706). Plasma levels of total adiponectin and leptin positively correlated with C-reactive protein (adiponectin: r = 0.277; P = 0.001; leptin: r = 0.248; P = 0.007) and troponin-I (adiponectin: r = 0.219; P = 0.001; leptin: r = 0.190; P = 0.025). Plasma levels of both adipocytokines have shown an inverse correlation with markers of platelet activation such as platelet glycoprotein VI (adiponectin: r = -0.120; P = 0.048; leptin:r = -0.205; P = 0.036), and in a negative trend with P-selectin (adiponectin: r = -0.116; P = 0.073; leptin: r = -0.172; P = 0.078). To support our findings, we determined high-molecular-weight adiponectin in a subgroup of 37 patients, which showed similar results. Increased concentrations of total adiponectin and leptin were associated with ACS. Intriguingly, high plasma levels of both adipocytokines seem to modulate platelet activation. Further studies should elucidate the adipocytokine regulation in CAD.