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Background: Diagnosis of the antiphospholipid syndrome (APS) is difficult as a result of limited specificity of existing assays for detecting clinically relevant antiphospholipid antibodies. Anti‐beta2‐glycoprotein I (beta2GPI) antibodies play a central role in the disease process of APS. Objectives: We have investigated the relation between antiphospholipid antibodies with specificity for domain I of beta2GPI and thrombosis/pregnancy morbidity in an international multicenter study. Patients/methods: Four hundred and seventy‐seven patients derived from nine different centres met the inclusion criterion of having anti‐beta2GPI antibodies in their plasma/serum. Clinical data and results of tests for lupus anticoagulant, anti‐cardiolipin antibodies and anti‐beta2GPI antibodies were established at the different centres of inclusion. After being re‐tested for the presence of IgG and/or IgM anti‐beta2GPI antibodies, the samples …