Hemophilia is an X-linked bleeding disorder, characterized by low plasma levels of coagulation factor VIII (FVIII) (hemophilia A) or FIX (hemophilia B). Because of this, hemophilia patients (HP) were considered as naturally-anticoagulated and therefore protected from thrombosis. Over the last decades hemophilia care underwent striking changes by the introduction of prophylaxis with repeated injections of standard or modified coagulation factor products that maintain steady-state trough levels of the deficient factor. Meanwhile, new medications, not based on replacement therapy, were developed (i.e., emicizumab and others). However, emicizumab (the only licensed drug) can be used only for prophylaxis; during acute bleeding or surgery, HP require additional therapies, supplementing emicizumab with FVIII/IX concentrates or with bypassing agents (e.g., recombinant activated FVII or activated prothrombin complex concentrate). Owing to the new therapeutic strategies, the hemostatic competency of HP is now much better assured than in the past and therefore their life expectancy is considerably improved. Furthermore, the combined effects of the improved life-expectancy and of the steady-state hemostatic competence achieved by prophylaxis, make HP to be near(normal). They are, therefore, liable to be affected by the circumstantial risk factors of venous thromboembolism (VTE) that are common in the general population. Furthermore, HP undergo frequent surgery/invasive procedures (especially major orthopedic surgery) when they are treated with coagulation factor concentrates or bypassing agents that may increase the risk of post-operative VTE. Therefore, one wonders if HP should be considered for perioperative antithrombotic prophylaxis to prevent postoperative VTE.Clinical data on the value of antithrombotic prophylaxis in this setting are scanty. Indeed, data from an observational multicentre prospective study of 46 HP who underwent orthopedic surgery concluded that the prevalence of postoperative symptomatic VTE was similar to that estimated in the general population. Multicenter prospective trials are warranted to address the value of antithrombotic prophylaxis to avoid post-operative VTE in HP, especially during major surgery when regular prophylaxis is supplemented with additional coagulation factor products or bypassing agents. Until this information is available, HP undergoing major surgery whilst on antihemorrhagic prophylaxis supplemented with coagulation factor concentrates or bypassing agents, should at least receive intermittent pneumatic compression.