The objectives of this study were to estimate the prevalence of IgA anticardiolipin antibodies (aCL) and anti-β₂-glycoprotein 1 antibodies (aβ₂-GPl) in a large number of patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (PAPS) and to examine possible associations between the clinical manifestations of the APS and the levels of IgA aCL and aβ₂-GPl. We also assessed the operative characteristics of IgA aCL and aβ₂-GP1. We retrospectively studied 130 patients with SLE and 35 patients with PAPS. In all patients we measured IgG, IgM, and IgA aCL and aβ₂-GP1 and recorded any of the clinical manifestations of the APS. IgA aCL were positive in 8.5% of patients with SLE and in 40% of patients with PAPS. Positive IgA aβ₂-GP1 were found in 17.7% of patients with SLE and in 25.7% of patients with PAPS. IgA aCL were associated with a history of venous thrombosis, thrombocytopenia, and recurrent fetal loss. In contrast, we could not establish significant associations between IgA aβ₂-GP1 and any of the clinical manifestations of the APS. Measurement of the IgA in addition to IgG and IgM aCL hardly changed the operative characteristics of aCL testing, while measurement of the IgA in addition to IgG and IgM aβ₂-GP1 increased sensitivity but with a greater loss in specificity. IgA aCL is significantly associated with more than one of the clinical manifestations of the APS in contrast to the IgA aβ₂-GP1. Routine measurement of the IgA isotype of both aCL and aβ₂-GP1 does not improve the operative characteristics of aCL and aβ₂-GP1 and therefore is not recommended at present.