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Abstract Objectives  The objective of this study were (1) to evaluate the prevalence of anti-annexin II antibodies in patients with various autoimmune diseases and antiphospholipid syndrome and (2) to correlate anti-annexin II antibodies with anti-phospholipid antibodies. Materials and Methods  Anti-annexin II antibodies and anti-phospholipid were detected, using an enzyme-linked immunosorbent assay, in the serum of patients with primary antiphospholipid syndrome (n = 16), systemic lupus erythematosus (n = 53), primary Sjögren syndrome (n = 71), systemic sclerosis (n = 17), systemic vasculitis (n = 18), and rheumatoid arthritis (n = 119). Healthy blood donors (n = 99) were used as controls. Results  Anti-annexin II antibodies were significantly more prevalent in patients with connective tissue diseases (8.5%), especially antiphospholipid syndrome (14.8%) and rheumatoid arthritis (10%), than in controls (2%). An inverse correlation was observed between anti-annexin II antibodies and antiphospholipid antibodies. Conclusion  Annexin II can be recognized by antibodies in serum from patients with systemic autoimmune disorders. Further studies are required to determine the clinical significance of anti-annexin II antibodies in rheumatoid arthritis and to determine their diagnostic value in discriminating clinical subgroups of patients with antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]