Antiphospholipid syndrome (APS) is a distinct clinical entity characterized by arterial and venous thromboembolic events, recurrent fetal loss and the presence of antiphospholipid antibodies in the patients' sera. In primary APS, there is no detectable underlying disease, while overlap APS is associated with clinical syndromes including systemic autoimmune diseases, infections, or malignancies. We carried out a retrospective analysis of serological and clinical manifestations as well as assessed outcome-measures in 165 patients with primary APS. Thrombotic manifestations and possible signs of autoimmune diseases were determined at the time of the diagnosis, followed by the analysis of recurrent thrombotic events and effects of therapy during the follow-up period. Among the 165 patients with primary APS at onset, 105 patients (63%) remained primary APS after a mean 5.2 years of follow-up. In 14% of the patients, subsequently APS became associated with various characteristics of undifferentiated connective tissue disease. Finally 23% of patients evolved into a definitive systemic autoimmune disease during a mean 9.75 years of follow-up. Recurrent thrombotic events were registered in 24% of patients. Our results suggest that primary APS may be considered as a potential early phase of a dynamic transition towards a well-defined systemic autoimmune disease.