Although the life expectancy of beta-thalassemia patients has markedly improved over the last few years, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events, mainly in beta-thalassemia intermedia, has led to the identification of a hypercoagulable state in these patients. In this review, the molecular and cellular mechanisms leading to hypercoagulability in beta-thalassemia are highlighted, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemia. Recommendations for thrombosis prophylaxis in these patients are also discussed.