Chronic inflammation plays a role in all stages of atherosclerosis leading to coronary artery disease (CAD), with elevated inflammatory markers being associated with the worse clinical outcome. The goal of the current study was to examine possible association between pro-inflammatory/pro-coagulant factors; anticardiolipin (aCL) autoantibodies, complement C3, C4 and leptin, and the severity of CAD expressed as SYNTAX score. Patients with symptoms of cardiac ischemia undergoing coronary angiography were recruited, and their blood levels of aCL-IgG, aCL-IgM, complement C3, C4 and leptin were assessed. Their association with the SYNTAX score, calculated based on coronary angiography findings, was analyzed. All patients had aCL antibody titer within the normal range. A significant positive association was found for aCL-IgG and SYNTAX score. Male patients had higher average aCL-IgG concentration and SYNTAX score than female patients. No association was found between SYNTAX score and C3 and C4. On the other hand, leptin was negatively associated with SYNTAX score. Our study demonstrates an association between the extent of CAD and aCL-IgG even in the absence of systemic autoimmune disease and at the aCL-IgG levels that are within the normal range. Also, association of lower leptin levels with more severe CAD suggests that its pro-inflammatory effects might not contribute to the pathogenesis of CAD, and that leptin might even exert protective effects on coronary vasculature.