One hundred and three consecutive asymptomatic anti-phospholipid (aPL) antibody-positive carriers, taking aspirin (n=75) or not (n=28), were studied retrospectively to determine whether aspirin could provide primary prevention of anti-phospholipid syndrome (APS) symptoms. All patients positive for anti-cardiolipin antibodies (aCL; >25 UGPL or UMPL) and/or lupus anti-coagulant were followed for a mean of 64+/-24.7 months.Among aPL-positive patients, 37 had systemic lupus erythematosus (SLE), 20 had prolonged activated partial thromboplastin times, 19 had other connective tissue diseases, 16 had autoimmune thrombocytopenia (AIT), 11 had diverse diseases. Nineteen patients experienced thrombotic event(s) during follow-up. Clinical features, biological parameters and hydroxychloroquine use were comparable for the two groups, but thrombotic events differed (log-rank test; P=0.02). Four of the 10 SLE patients not taking aspirin developed thrombosis compared with 3/27 SLE patients taking aspirin (log-rank test; P=0.03). Anti-phospholipid -positive patients with AIT developed fewer thromboses while taking aspirin (log-rank test; P=0.01). In conclusion, aPL-positive SLE and AIT patients should take aspirin to prevent APS manifestations. Prospective therapeutic trials are needed to confirm aspirin's prophylactic role in such patients.