ABSTRACT Antiphosphatidylethanolamine (aPE) autoantibodies are associated with clinical symptoms of antiphospholipid syndrome (APS). However, the clinical significance of aPE remains to be fully established. In an effort to define aPE, we discovered that aPE actually consists of two distinctive subtypes. This notion is based on our findings that there are two types of aPE antibodies – cofactor-independent (aPEi) and cofactor-dependent (aPEd), which have different antigens and pathogenic mechanisms. In the current effort, we will investigate the clinical characteristics of aPE subtypes in a retrospective study by testing the hypothesis that aPEi and aPEd antibodies have different associations with the clinical and laboratory criteria for APS. The new knowledge will help define and differentiate the two subtypes of aPE, with potentially important implications on diagnosis and patient care.