Immune mechanisms play a critical role in cardiovascular disease. Cardiolipins are candidate autoantigens with a prothrombotic activity of their corresponding antibodies. We investigated the influence of pre-existing immunoglobulin (Ig)M and IgG anticardiolipin (aCL) antibodies on restenosis after coronary balloon angioplasty and their interaction with tissue plasminogen activator, plasminogen activator inhibitor type-1, von Willebrand factor and lipoprotein (a) in 132 patients with stable angina pectoris using immunoassays. Thirty percent of patients developed angiographically proven restenosis estimated by three independent experienced angiographers; 12% of all patients developed recurrent restenoses at the same site during a follow-up period of 2 years. Circulating IgM aCL antibodies categorized by quartiles predicted recurrent restenoses (logistic regression, for trend P < 0.04) with an increase of relative risk (RR) per quartile of 2.09. The predictive value of IgM aCL antibodies was unchanged adjusting for established cardiovascular risk factors (P = 0.028, RR = 2.69), extent of coronary artery disease (P = 0.014, RR = 2.73) and inflammatory parameters (P = 0.025, RR = 2.79), but lost significance adjusting for other prothrombotic parameters (P = 0.24, RR = 1.76). IgM aCL antibodies positively correlated with lipoprotein (a) (r = 0.23, P = 0.04). However, there was no significant interaction between their influences on recurrent restenoses. The other prothrombotic parameters did not predict single or recurrent restenoses. In conclusion, IgM aCL antibodies may help to identify a group of patients at high risk for recurrent restenoses after coronary balloon angioplasty.