Premature atherosclerosis has been recognized as a major co-morbid condition in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the effect of tPA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor) antigen concentrations and 4G/5G polymorphism of the PAI-1 gene on the development of atherosclerosis in SLE patients. One hundred and six SLE patients, 28 Takayasu arteritis (TA) patients and 98 healthy control subjects (HCs) were studied. PAI-1 and tPA antigen levels were measured by ELISA method. PAI-1 gene polymorphism was determined by using allele-specific PCR method. SLE patients had a significantly higher frequency (22.6%) of plaque (p=0.01) and higher IMT (p=0.04) compared with HCs respectively. Only age at disease onset was associated with plaque formation in multivariate regression analysis (p=0.001). Plasma tPA ag levels in SLE patients were significantly higher compared with HCs (p=0.005) and PAI-1 ag levels were significantly higher compared with TA patients (p=0.03). There were no significant differences between study groups in both genotype distribution and allele frequencies of PAI-1 gene, but SLE patients with 4G/4G genotype had higher IMT (p=0.02) calcium scoring (p=0.006) compared with 4G5G/5G5G genotypes. The present study suggests that measuring fibrinolytic parameters would have little additional benefit beyond traditional and novel risk factors in predicting coronary artery disease (CAD). Lupus (2011) 20, 1063-1071.