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Antiphospholipid antibodies (aPL) have been implicated in the pathogenesis of coronary artery disease (CAD). We evaluated the presence of aPL in patients with chest pain/acute coronary syndromes (ACS) to determine if aPL were associated with the presence and severity of CAD, adverse outcomes, and other coronary risk factors. Patients with chest pain/ACS were evaluated for aPL prior to diagnostic and therapeutic investigations. Coronary angiograms were graded according to the severity of disease. Risk factors, including family histories, were assessed and patients were followed for adverse outcomes. To date, 232 patients (116 M, 116 F, mean age 63 years) with a mean follow-up of 9 months were studied. Thirty-seven percent (86/232) were positive for one or more aPL. More women, 49/86 (57%), were aPL positive versus men, 37/86 (43%). The presence of aPL appeared associated with both presence and severity of CAD (P = 0.176 women; P = 0.163 men). In patients undergoing procedures (angioplasty, stent, bypass), aPL was significantly associated with both an increase in adverse cardiac outcomes (P = 0.045) and extracardiac thrombotic events (P = 0.033). Anti-beta2 glycoprotein-1 (abeta2GP1) was the most frequent aPL, occurring in 68.5% of aPL-positive patients with CAD. Anticardiolipin antibody (aCL) occurred in only 7.4%. IgM isotypes were the most frequent for all categories of aPL (range 55-90%). Family history of antiphospholipid syndrome (APS)-related events was more significant in aPL-positive than aPL-negative individuals (P = 0.027).