The discovery of antiphospholipid antibodies (aPL) positivity in individuals who have never experienced thrombosis or pregnancy complications is not a rare event, and is one of the unresolved issues in the field of antiphospholipid syndrome (APS). This paper focuses on primary prophylaxis for thrombotic events in aPL carriers. In our view, patients with high risk aPL profiles and/or other cardiovascular risk factors, concomitant diagnosis of systemic lupus erythematosus (SLE) and patients with an history of obstetric APS (OAPS) should be offered thromboprophylaxis. Chronic thromboprophylaxis with low-dose aspirin and hydroxychloroquine in aPL positive SLE patients should be prescribed both to prevent thrombosis and to avoid early organ damage.