Apelin and ghrelin have emerged as novel adipokines, but their role in coronary artery disease (CAD) remains obscure. In the present study, we analyzed their serum levels in patients with acute coronary syndromes (ACS) or established asymptomatic CAD. A total of 355 participants were enrolled. Among them were 80 patients with unstable angina (UA) and 115 patients with acute myocardial infarction (AMI) hospitalized in the coronary care unit. We also included 88 asymptomatic patients with established CAD (asymptomatic CAD) and 72 age-and sex-matched healthy controls (HCs). All groups with CAD underwent coronary angiography, and the Gensini score was determined. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), as well as apelin and ghrelin were assayed. Patients with ACS (UA or AMI) were sampled at hospital admission. All 3 groups with CAD (UA, AMI, or asymptomatic CAD) showed significantly higher levels of hsCRP, HOMA-IR, and white blood cells than controls (P < 0.01). Conversely, apelin and ghrelin concentrations were considerably (P < 0.05) lower in CAD patients with respect to the control group. Most importantly, UA (6.72 +/- 3.51 ng/mL) and AMI (6.02 +/- 4.07 ng/mL) groups had even lower apelin levels on admission compared with the asymptomatic CAD group (13.53 +/- 5.2 ng/mL) (P < 0.05). Logistic regression analysis showed an independent association of low apelin and ghrelin levels with CAD presence. Besides this result, apelin showed an inverse relationship with ACS incidence and a Gensini score independent of other cardiovascular risk factors (P < 0.05). In conclusion, CAD seemed to correlate with low serum apelin and ghrelin levels. Moreover, apelin concentrations inversely were associated with the severity and the acute phase of CAD, which suggests its involvement in the progression and destabilization of coronary atherosclerotic plaques.