AbstractObjective. To investigate whether anticardiolipin antibodies (aCL) in patients with systemic lupus erythematosus (SLE) bind to β2‐glycoprotein I (β2GPI), and to search for a relationship between the presence of IgG and/or IgM anti‐β2GPI antibody and clinical manifestations in SLE patients.Methods. IgG and IgM anti‐β2GPI in 308 Japanese SLE patients were measured using phospholipid‐independent enzyme immunoassays. Relationships to clinical histories and to various laboratory data were examined.Results. The values of anti‐β2GPI and aCL, as measured by conventional enzyme immunoassay, showed a strong correlation, but the anti‐β2GPI assay was more useful in distinguishing β2GPI‐dependent aCL from β2GPI‐independent aCL. The presence of IgG anti‐β2GPI was associated with an increased frequency of a history of thrombosis. Comparisons of various laboratory data suggested that the titer of anti‐β2GPI may fluctuate with disease activity.Conclusion. The results suggest that pathogenic aCL is directed against structurally altered β2GPI and that enzyme immunoassay for anti‐β2GPI may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE.